CN103068308B

CN103068308B - For the lower pressure environment of fluid conveying device

Info

Publication number: CN103068308B
Application number: CN201180040283.7A
Authority: CN
Inventors: K·肖特
Original assignee: Seventh Sense Biosystems Inc
Current assignee: Excellent biological health Co.
Priority date: 2010-07-16
Filing date: 2011-07-15
Publication date: 2016-03-16
Anticipated expiration: 2031-07-15
Also published as: EP2593014A1; US20130081960A1; WO2012009613A1; JP2013538069A; ES2561824T3; CN103068308A; EP2593014B1; US20120016308A1; US8561795B2; US20190023473A1

Abstract

The application relates generally to a kind of device, and this device is used for from the skin of experimenter and/or extracts material below this skin, and/or is used for transportation of substances to the skin of experimenter and/or the position below this skin.One or more skin that this device comprises such as pin or microneedle inserts object and one or more vacuum chamber, and this vacuum chamber has the internal pressure being less than atmospheric pressure.This device is comprised in the environment that can help to maintain this pressure.Such as, the encapsulation comprising this environment also can have the pressure being less than atmospheric pressure, and/or this encapsulation can be molded into this device or have the shape not comprising a large amount of gas in addition, this large amount of gas " can to leak " in this device and to change the pressure of vacuum chamber.

Description

For the lower pressure environment of fluid conveying device

Related application

This application claims the U.S. Provisional Patent Application No.61/365 being entitled as " Low-PressurePackagingforFluidDevices " of the Schott that 16 days July in 2010 incorporated herein by reference submits to, the rights and interests of 196.

Technical field

Present invention relates in general to system and method, this system and method is used for carrying and/or receiving fluid (such as, passing through skin) from experimenter, comprises the encapsulation with this system relationship.

Background technology

There is multiple technologies and method, this techniques and methods is used for sensing and be exposed in response to experimenter its situation, comprises the sensing of mammiferous physiological situation and/or surrounding.There is other technology be used for from mammal withdrawn fluid (such as blood).Although many this technology are applicable to multiple object, the technology with one or more feature of the motility of simplicity and the use such as increased will be favourable.

Summary of the invention

Present invention relates in general to system and method, this system and method is used for carrying and/or receiving fluid (such as, passing through skin) from experimenter, comprises the encapsulation with this system relationship.In some cases, theme of the present invention relates to relevant product, the special replacement scheme of problem and/or the multiple different purposes of one or more system and/or article.

In one aspect, the present invention relates to a kind of article.According to one group of embodiment, these article comprise the environment that pressure is less than the about 50mmHg of below atmospheric pressure, wherein this environment device.In some cases, this device comprises one or more skin and inserts object, this skin inserts object and is used for from the skin of experimenter and/or extracts material below this skin, and/or is used for transportation of substances to the skin of experimenter and/or the position below this skin.

In another group embodiment, these article can relate to the device be comprised in encapsulation, and wherein this wrapper is containing the first volume limited by the device be included in wherein and the second volume limited by the outside of this device.In some cases, the second volume can be no more than about 25% of the first volume.In certain embodiments, this device can comprise one or more skin and insert object, this skin inserts object and is used for from the skin of experimenter and/or extracts material below this skin, and/or is used for transportation of substances to the skin of experimenter and/or the position below this skin.

In another group of embodiment, these article relate to the device be comprised in encapsulation, and wherein this wrapper is containing the first volume limited by the device be included in wherein and the second volume limited by the outside of this device.In certain embodiments, the second volume can have the volume of at least about 50% of the first volume.In some cases, this device can comprise one or more skin and insert object, this skin inserts object and is used for from the skin of experimenter and/or extracts material below this skin, and/or is used for transportation of substances to the skin of experimenter and/or the position below this skin.

In another group of embodiment, these article can comprise the device be included in encapsulation, and this encapsulation is molded into this device substantially.In some cases, this device comprises one or more skin and inserts object, this skin inserts object and is used for from the skin of experimenter and/or extracts material below this skin, and/or is used for transportation of substances to the skin of experimenter and/or the position below this skin.

Another aspect of the present invention relates to a kind of method.According to one group of embodiment, the method comprises action device being exposed to environment, and this environment has the pressure being less than the about 50mmHg of below atmospheric pressure.In certain embodiments, this device comprises one or more skin and inserts object, this skin inserts object and is used for from the skin of experimenter and/or extracts material below this skin, and/or is used for transportation of substances to the skin of experimenter and/or the position below this skin.

On the other hand, the present invention relates to a kind of method manufacturing one or more embodiment described herein.On the other hand, the present invention relates to a kind of method using one or more embodiment described herein.

When considered in conjunction with the accompanying drawings, from the following detailed description of various non-limiting example of the present invention, other advantage of the present invention and novel feature will become obvious.When this description and by reference the document that is incorporated to comprise conflict and/or the disclosure of contradiction, this description will be top dog.If two or more documents be incorporated to by reference comprise disclosure that is that collide with one another and/or contradiction, then the document with slower expiration date will be top dog.

Accompanying drawing explanation

Describe non-limiting example of the present invention with reference to accompanying drawing by the mode of example, this accompanying drawing is schematic and does not expect and draw in proportion.In the drawings, each the identical or almost identical parts illustrated typically are represented by single Reference numeral.For the sake of clarity, be not that each parts is marked in each figure, also not shown each embodiment of the present invention each parts (when illustrate for permission those skilled in the art understand the present invention be unnecessary).In the drawings:

Figure 1A-1B illustrates the device according to some embodiment of the present invention;

Fig. 2 A-2C illustrates device according to various embodiments of the present invention;

Fig. 3 illustrates the device had in one embodiment of the present of invention of vacuum chamber; And

Fig. 4 A-4C illustrates the various devices be closed in a package according to other embodiment other of the present invention.

Detailed description of the invention

Present invention relates in general to system and method, this system and method is used for carrying and/or receiving fluid (such as, passing through skin) from experimenter, comprises the encapsulation with this system relationship.Some aspect of the present invention relates generally to device, and this device is used for from the skin of experimenter and/or receives material below this skin, and/or is used for transportation of substances to the skin of experimenter and/or the position below this skin.In certain embodiments, this device can comprise one or more mass transfer parts, such as pin or microneedle.In some cases, this device can also comprise one or more vacuum chamber, and such as, the internal pressure of this vacuum chamber is less than atmospheric pressure.In some respects, this device can be contained in the environment that can help to maintain this pressure.Such as, the encapsulation comprising this environment also can have the pressure being less than atmospheric pressure, and/or this encapsulation can be molded into this device or have the shape not comprising a large amount of gas in addition, this large amount of gas " can to leak " in this device and to change the pressure of any vacuum chamber that wherein may comprise.In certain embodiments, the pressure of environment can be same as or be less than the pressure of the vacuum chamber comprised in this device.Other side of the present invention relates generally to the method producing this device, uses the technology of this device, relates to the tool set of this device, etc.

As mentioned, one aspect of the present invention relates generally to the environment for comprising device, and this device can have vacuum chamber, and the internal pressure of this vacuum chamber is less than ambient atmospheric pressure (about 101kPa, or about 760mmHg).Should be appreciated that atmospheric pressure can change slightly, but substantially near these values.

The example comprising this device of vacuum chamber is discussed in more detail below.In one group of embodiment, the environment comprising this device also can have the pressure being less than atmospheric pressure.Such as, this environment can have at least approximately 50mmHg less of atmospheric pressure, at least approximately 100mmHg, at least approximately 150mmHg, at least approximately 200mmHg, at least approximately 250mmHg, at least approximately 300mmHg, at least approximately 350mmHg, at least approximately 400mmHg, at least approximately 450mmHg, at least approximately 500mmHg, at least 550mmHg, at least 600mmHg, at least 650mmHg, at least approximately 700mmHg, or the pressure of at least about 750mmHg.

In certain embodiments, the pressure in this environment can be substantially identical to or be less than in this device the pressure of any vacuum chamber comprised.When not wishing by any theory constraint, can believe, be same as by the pressure of the environment making this device of encirclement or even lower than the internal pressure in vacuum chamber, gas can be reduced at least in part to " leakage " in the vacuum chamber in this device or diffusion.Therefore, such as, the lower ambient pressure surrounding this device can reduce the internal pressure in the vacuum chamber that comprises in this device along with the past of time.

Can be produced by any suitable technology or maintain the pressure of the environment surrounding this device.In one group of embodiment, this environment is comprised in encapsulation in the mode of partially or even wholly surrounding this device.This encapsulation can be formed by any suitable material, and in some cases, is formed by the impermeable material of gas substantially.Such as, this encapsulation can be formed by following material: glass, the metal of such as rustless steel or aluminum (such as, as rigid metal encapsulation or as deformable paper tinsel, such as, aluminium foil), polymer (such as, Merlon, polyvinylidene chloride (PVDC) or Saran packaging film, polypropylene (PP), polyolefin, nylon, the such as polyethylene of Low Density Polyethylene (LDPE) or high density polyethylene (HDPE) (HDPE), polyester (PET)), laminated material (such as, the laminated material of metal and polymer), metallized film or paper tinsel, mylar, Ofoil ^tM48, etc.Ofoil ^tM48 is can from Oliver-TolasHealthcarePackaging(GrandRapids, MI) the laminated web material that obtains and bag-shaped laminated material.Such as, in one embodiment, this encapsulation is formed by the aluminium foil being laminated to inner polymeric layer.This encapsulation can be can manual deformation (such as, without auxiliary, not using instrument), or in some cases, this encapsulation can be rigidity and can not manual deformation.Such as, this encapsulation can be hard " housing " or the box that comprise this device or at least its part, or this encapsulation can be the sack surrounding this device.

In one group of embodiment, this encapsulation has the shape substantially the same with the device comprised in this encapsulation, such as, due to wherein relatively low pressure.Therefore, at least in some cases, the shape of this encapsulation can be molded in around the device that wherein comprises substantially.Such as, this encapsulation can by not having predefined shape inherently (such as, sack) material formed, but by this material package around this device with after producing low pressure wherein, this material to this device, is therefore formed the shape (due to relative to pressure differential this material of atmospheric pressure in) substantially the same with this device by " maintenance ".But in other embodiments, this encapsulation can be formed by rigid material, but be formed as the shape (such as, predefined shape) substantially the same with this device.

In certain embodiments, what this encapsulation can have a volume of the device comprised in this encapsulation is no more than about 50%, be no more than about 25%, be no more than about 20%, be no more than about 15%, be no more than about 10%, be no more than about 5%, be no more than about 3%, be no more than about 1%, or be no more than the volume of about 0.5%, thus this is provided to be encapsulated in closely cooperating or being molded around this device.But in other embodiments, the volume of this encapsulation can be more much bigger than the volume of the device comprised in this encapsulation.Such as, the volume of this encapsulation can be at least about 50%, at least about 75%, at least about 100%, at least about 150%, at least about 200%, at least about 300%, at least about 400%, at least about 500%, at least about 600%, at least about 700%, at least about 800%, at least about 900% or at least about 1000% of the volume of the device comprised in this encapsulation.In one embodiment, the volume of this encapsulation is no more than about 2000% or about 1000% of the volume of the device comprised in this encapsulation.

In certain embodiments, can keep the pressure in this encapsulation due to the composition of this encapsulation, such as, this encapsulation can be formed by the impermeable material of gas substantially, makes outside (environment) air small leaks or does not leak in this encapsulation.Therefore, such as, this material is for 0 ₂, N ₂, C0 ₂and/or H ₂the permeability of 0 can be less than about 2000cm ³mm/ (m ²bATIAN) (for having with m ²for the given area of unit, the thickness in units of mm, and Israel and Palestine are the material of the pressure differential of this material of leap of unit, and gas is with cm ³/ sky is unit flowing), be less than about 1500cm ³mm/ (m ²bATIAN), be less than about 1000cm ³mm/ (m ²bATIAN), be less than about 900cm ³mm/ (m ²bATIAN), be less than about 800cm ³mm/ (m ²bATIAN), be less than about 700cm ³mm/ (m ²bATIAN), be less than about 600cm ³mm/ (m ²bATIAN), be less than about 500cm ³mm/ (m ²bATIAN), be less than about 400cm ³mm/ (m ²bATIAN), be less than about 300cm ³mm/ (m ²bATIAN), be less than about 200cm ³mm/ (m ²bATIAN), be less than about 100cm ³mm/ (m ²bATIAN), be less than about 90cm ³mm/ (m ²bATIAN), be less than about 80cm ³mm/ (m ²bATIAN), be less than about 70cm ³mm/ (m ²bATIAN), be less than about 60cm ³mm/ (m ²bATIAN), be less than about 50cm ³mm/ (m ²bATIAN), be less than about 40cm ³mm/ (m ²bATIAN), be less than about 30cm ³mm/ (m ²bATIAN), be less than about 20cm ³mm/ (m ²bATIAN), be less than about 10cm ³mm/ (m ²bATIAN), or be less than about 5cm ³mm/ (m ²bATIAN), etc.In other embodiments, effective technology can be used to maintain pressure in this encapsulation, such as, use pump gas pump to be sent this encapsulation (this pump can run off and on or continuously, etc.).

Any appropriate technology may be used for the pressure producing and/or maintain the environment surrounding this device.Such as, the such as vacuum pump of rotating blade pump, membrane pump, liquid rotary pump, piston pump, screw pump, vortex pump, Wankel pump, external blade pump, Toepler pump or lobe pump may be used for the pressure reducing the environment surrounding this device.Many this vacuum pumps commercially can obtain, and by different manufacturers for being applied to different purposes.Such as, in one group of embodiment, device is placed in encapsulating material, and then, the gas in encapsulating material such as uses pump to be removed, and therefore causes encapsulating material collapse and substantially himself is molded on the outer surface of this device.In another group embodiment, this device can be placed on such as MultiVacC100(Multivac, KansasCity, MO) vacuum packaging machine in, this vacuum packaging machine may be used for producing and surrounds the vacuum of this device.

Although medical treatment device is often encapsulated in gnotobasis, namely enter in the material of the ability of this medical treatment device in the microorganism prevented or at least reduce such as antibacterial or virus, but this encapsulation does not comprise the environment that pressure reduces usually, namely has the environment of the pressure being less than atmospheric pressure.The encapsulation that can maintain this pressure must be airtight and for such as 0 ₂(oxygen), N ₂(nitrogen), He(helium) etc. gas be substantially impermeable, instead of be only substantially impermeable for microorganism, this all will cause reducing losing of pressure environment, even if maintain aseptic because any gas transmission to be less than to pressure in the environment of atmospheric pressure.The size of gas, than a size decimal order of magnitude of microorganism, makes integrity demands stricter accordingly.Therefore, for microorganism substantially impermeable encapsulating material be also not necessarily substantially impermeable concerning gas.In addition, for the application of most prior art medical treatment device, the environment that pressure reduces is undesirable, and this is that this also can cause microorganism to be introduced in this encapsulation because the small destruction of the integrity of even this encapsulation will cause gas to flow in this encapsulation.Therefore, medical treatment device is not typically encapsulated in the environment of the pressure reduction with the pressure being less than atmospheric pressure.

A non-limitative example of this encapsulation is illustrated in Figure 4 A.In this drawing, device 1310 is comprised in encapsulation 1300.Encapsulation 1300 is rigidity encapsulation in this embodiment, although in other embodiment such as shown in Fig. 4 B and 4C, encapsulation 1300 can be flexible or deformable.In this embodiment, encapsulation 1300 comprises the environment with pressure P 2 wherein, and this pressure may be less than outside (environment) pressure P 3 in certain embodiments.

What comprise in encapsulation 1300 is device 1310, and this device comprises supporting construction 1301, one or more mass transfer parts 1302, pressure regulator 1303, sensor 1304, signal or display device 1305 and device activation members 1306.Such as, mass transfer parts can comprise one or more microneedle as shown in Fig. 4 A.Activation members can be configured to and be arranged to cause mass transfer component exposed to skin when the startup of activation members.Such as, device activation members 1306 can be the button, rotating disk, switch etc. as shown in Fig. 4 A.

In this embodiment, pressure regulator 1303 comprises the vacuum chamber with the first pressure P 1.Pressure P 1 in device 1310 can be same as or be less than the pressure P 2 in encapsulation 1300, although in other embodiments, pressure P 1 can be greater than pressure P 2.If pressure P 1 is substantially equal to pressure P 2, then will there is not Leakage Gas or be diffused in surrounding or leave pressure regulator 1303 to the tendency in surrounding.If pressure P 1 is less than pressure P 2, some gases may have the tendency be diffused in pressure regulator 1303, and if pressure P 1 is greater than pressure P 2, then some gases can have the tendency be diffused into outside pressure regulator 1303.

Another embodiment is shown in figure 4b, although in this example, can the material of manual deformation is used as encapsulation 1300(such as, sack or pouch) to comprise device 1310, instead of the rigidity encapsulation as shown in Fig. 4 A.Encapsulation 1300 can not have predefined shape, but owing to encapsulating pressure (pressure P 2) in 1300 relative to the difference of outside (environment) pressure P 3, substantially can present the external shape of this device.Such as, when pressure P 2 is less than pressure P 3, ambient exterior atmospheric pressure can force encapsulation 1300 to present substantially identical with the shape of device 1310 shape.

This device as shown in this figure is similar to the device discussed above with reference to Fig. 4 A.Such as, device 1310 can comprise pressure regulator 1303, and this pressure regulator has pressure P 1 wherein.Pressure P 1 in device 1310 can be same as or be less than pressure P 2, although in other embodiments, pressure P 1 can be greater than pressure P 2.Fig. 4 C is similar to Fig. 4 B, except in this example, has added rigid material 1307 to comprise at least in part and/or bracing or strutting arrangement 1310.This rigid material may be used for such as protector 1310 and, from mechanical impacts or manipulation, and/or prevents the accidental activation (such as, if device activation members 1306 is by accident collision) of this device by device activation members 1306.Such as, rigid material 1307 can have the shape of guard shield, plate, housing etc.Describe in example as shown in Fig. 4 C, rigid material 1307 can be formed as the ingredient of encapsulation 1300 and/or device 1310, and/or rigid material 1307 can be the separating component comprised in encapsulation 1300.In some cases, rigid material just can obtain the final vacuum lower than independent flexible package after this encapsulation of sealing.

In some cases, environment also can be substantially aseptic.Such as, this encapsulation can by being formed by pasteurization material.Such as, this material can tolerate conditions for sterilization and significantly not degenerate.Such as, this material can tolerate one or more of disinfection technology, such as chemical substance, radiation (such as, by ultraviolet light and/or ionizing radiation), heat treatment etc.Suitable disinfection technology and scheme are known to those skilled in the art.Such as, in one embodiment, this material is autoclavable, that is, this material can tolerate conventional autoclave conditions (such as, usually under high pressure, the gauge pressure of such as at least one air, is exposed to the temperature being greater than about 100 DEG C or about 120 DEG C), make this material significantly can not be out of shape after sterilisation or become unavailable in addition, such as, become permeable gas and/or form hole.Other example of disinfection technology comprises and is exposed to such as bakelite, the chemical substance of alcohol or alcohol/aqueous mixtures (such as, isopropyl alcohol, isobutanol, ethanol etc.), halogen (such as, the chlorine dissolved, bromine etc.), iodine (such as, tincture), heavy metal (such as, silver nitrate etc.), quaternary ammonium compound, detergent, aldehyde (such as, formaldehyde, glutaraldehyde etc.), gas (such as, carbon dioxide, oxirane, ozone etc.) or radiation, such as ultraviolet radiation (such as, frequency with about 260nm), infra-red radiation, gamma ray, short wavelength or such as gamma ray, the high-level radiation of electron beam or X-ray.

It should be noted that sterilization can not necessarily completely.In some cases, such as, by suppress or killing microorganisms, can perform sterilization until exist viable microbial quantity at least about 10 ⁶minimizing.In certain embodiments, disinfecting process can be performed, until at least about 10 of the quantity of the viable microbial existed ⁷, in some cases at least about 10 ⁸, and in other situation at least about 10 ⁹minimizing.In certain embodiments, sterilization can be performed until the microorganism of work of all existence is substantially suppressed or kill in some manner, or make microorganism alive can not be detected after sterilisation.

In certain embodiments, oxygen scavenger may reside in this encapsulation, such as, is formed as the separating component comprised in the ingredient of this encapsulation and/or this encapsulation.In one embodiment, oxygen scavenger can be formed as the ingredient of the device comprised in this encapsulation.In one group of embodiment, oxygen scavenger can be deaerating membrane.Deaerating membrane comprises the film of PVDC coating, comprises polyvinyl alcohol (PVOH) as oxygen barrier layers, or uses vacuum-deposited aluminum to reduce to the Oxygen permeation of encapsulating products.Can easily obtain this deaerating membrane in the mode of business, such as, CSP-1940 and CSP-1941 can be obtained from CSPTechnologies, USA.Other example other comprises U.S. Patent No. 5,496, disclosed in 649 those.

Such as, this film can being mixed to form by each composition.Such as, the first composition can comprise oxidable baseset compound, poly-(ethylene methyl acrylate cyclohexenyl methyl acrylate) (EMCM).Except envelope alters agent and base polymer beyond the region of objective existence, the second composition can comprise masterbatch, and this masterbatch comprises transition-metal catalyst and non-ly migrates light trigger.Non-light trigger of migrating can allow packaging machine just to cause 0 before filling ₂remove mechanism, this can increase the active capacity removing composition.When ultraviolet radiation starts, polymer system can absorb residual 0 in capsule header space ₂(such as, by irreversible bonding), and/or other 0 of primary seal dress barrier layer may be penetrated ₂.

As mentioned, in some aspects, present invention relates in general to a kind of device, this device is used for receiving material from experimenter, such as, from the skin of experimenter and/or receive below this skin, and/or be used for transportation of substances to experimenter, such as, transportation of substances is to the skin of experimenter and/or the position below this skin.Here is the details of this device.In some cases, this device can with external apparatus interface to determine the analysis thing comprised in fluid that is that comprise in this device or that collected by this device.Such as, this device can on keeper mounted externally, and this device can comprise the port leaving this device for transporting fluid, and this device can comprise the window for inquiring about the fluid comprised in this device, etc.

Receive fluid can be any suitable body fluid, such as interstitial fluid, other skin associated materials, mucosa material or fluid, whole blood, perspiration, saliva, blood plasma, tear, lymph, urine, blood plasma, or other body fluid any or its combination.The material received from experimenter can comprise solid or semisolid material, such as skin, cell or other material any from experimenter.The material that can be transported to experimenter according to some embodiments of the present invention comprises diagnostic substances, the therapeutant of such as medicine, etc.Here when from or when being carried by skin or receive the fluid of such as blood, various embodiment of the present invention is described.Be to be understood that, in all embodiments here, no matter special exemplary language used (such as, receive blood), the apparatus and method of other embodiments of the invention can be used for from the skin of experimenter and/or receive any material below this skin, and/or be used for carrying any material to experimenter, such as, arrive the position below the skin of experimenter and/or this skin.Also should be appreciated that in some cases, face (such as, under the skin the fat deposit in face or Musclar layer in) fluid can be produced under the skin.Therefore, conveying and/or the description here of fluid that receives " in skin " are also appreciated that the layer that comprises in other embodiments and transporting fluid into immediately below skin and/or receive fluid from the layer immediately below skin.

In one aspect, present invention relates in general to the device that use has mass transfer parts (these mass transfer parts can comprise such as one or more microneedle and/or other skin insert object) be used for receiving from experimenter's (such as, from skin and/or below skin) or extracting the apparatus and method of blood or other body fluid.In certain embodiments, this device also can comprise locker room, and the internal pressure of this locker room was less than atmospheric pressure before reception blood or other body fluid.In some cases, a part for this device can pierce through the skin of experimenter, and can transport fluid into experimenter subsequently and/or receive fluid from experimenter.Experimenter is the mankind normally, although can nonhuman subjects be used in some cases, such as other mammal, such as Canis familiaris L., cat, horse, rabbit, milch cow, pig, sheep, goat, mouse (such as, Rattus norvegicus), mice are (such as, house mouse), Cavia porcellus, hamster, primate (such as, monkey, chimpanzee, baboon, ape, gorilla etc.) or analog.

In some cases, this device can be applied to skin, and is activated to receive fluid from experimenter.This device or its part can be processed to determine the analysis thing in this fluid and/or this fluid individually or by external equipment subsequently.Such as, fluid can be received in this device, and/or this device can comprise sensor or reagent, and this sensor or reagent can determine that this fluid and/or suspection are comprised in the analysis thing in this fluid.

In one group of embodiment, the present invention relates to the determination of the situation of experimenter.Can analysing body fluid and/or other material relevant to skin, such as, as the instruction in the past of experimenter, at present and/or in the future situation, or be used for determining the situation of experimenter outside.Such as, can visually, sense of touch ground, by abnormal smells from the patient, determined by instrument etc.Therefore, in an aspect, present invention relates in general to various device, described various device is used for conveying and/or from the skin of experimenter and/or receive blood or other body fluid below this skin.Therefore, in the following description, only by way of example blood is discussed, and in other embodiments, except and/or alternative blood, other fluid can be received from skin.

In one group of embodiment, this device comprises the mass transfer parts can carried or receive fluid from experimenter.As used herein, " mass transfer parts " promote that material or fluid move to another part from a part of this device, and/or move to the combination of experimenter or any parts conversely or parts from this device.Mass transfer parts can comprise the opening being configured to fluid to receive any size in this device and/or geometry.Such as, the opening of mass transfer parts can be arranged in two dimensional surface, or this opening can comprise three-dimensional chamber, hole, groove, slit etc.In certain embodiments, mass transfer parts also can comprise one or more microneedle or other skin inserts object, and this microneedle or other skin insert object and is disposed to such as cause fluid to be released from experimenter by the skin piercing through experimenter.

In certain embodiments, if fluid (such as, blood or interstitial fluid) is partially or even wholly filled surround the case that skin inserts object or other object, then this case can limit material transmission part at least partially.Mass transfer parts can comprise other suitable fluid carrier any or flowing activation members.Other parts comprising the passage, microfluidic channel, pipe, wicking member, Dewar vessel etc. partially or even wholly closed can be parts for mass transfer parts or mass transfer parts.

This fluid can from and/or be received by the skin of experimenter's (or other mucomembranous surface).Mass transfer parts can be such as one or more pin and/or microneedle, hygroscopic agent, cutter or other pierce through element, electric aid system etc., such as, as discussed in detail here.If use pin or microneedle, then they can be solid or hollow, namely blood or other fluid can in pin or microneedle and/or around advance in this device.In some cases, pin or microneedle also can such as remove from experimenter after being inserted in skin, such as, so that the flowing of the blood increased from experimenter or other fluid.In one group of embodiment, mass transfer parts comprise cup or the passage of the solid needle be removed from skin and the flowing being used for guide blood or other body fluid.

In some respects, this device can comprise the supporting construction of such as shell.As discussed here, this shell may be used for the surface of skin mass transfer parts being applied to experimenter, such as, fluid can be transferred and/or be received from the skin of experimenter.In some cases, shell can fixed substance transmission part, and mass transfer parts can not be moved relative to shell; But in other situation, mass transfer parts or its part can move relative to shell.In one embodiment, as non-limitative example, mass transfer parts are fixed relative to shell, and launch actuator arrangement make this device be applied in this device skin piercing through experimenter at least partially that skin causes mass transfer parts.In some cases, shell seal launches actuator.

In certain embodiments, the part launching actuator or expansion actuator can move to the second position from primary importance.Such as, primary importance can be not with contact skin (such as, the skin of mass transfer parts inserts object and can be contained in the depression of mass transfer parts) mass transfer parts be connected to the position of launching actuator, and the second position launching actuator can be the position of mass transfer component contact skin (such as, to pierce through skin).Any suitable technology can be used to move expansion actuator, such as, manually, mechanically, electromagnetically, use servo control mechanism etc.Such as, in one group of embodiment, by promoting the button on this device, launch actuator and can move to the second position from primary importance, this promotion causes expansion actuator to move (mechanism directly, or by being connected with expansion actuator by button).Can in conjunction with or alternative button use other mechanism (such as, rotating disk as discussed here, lever, slide block etc.).In another group embodiment, launch actuator and automatically can move to the second position from primary importance, such as by computer starting time, at remote activation time, after the past period etc.Such as, in one embodiment, be connected to the servo launching actuator and started electronically, expansion actuator is moved to the second position from primary importance.In some cases, launch actuator and can comprise the trigger mechanism starting and launch.

In some cases, expansion actuator and/or mass transfer parts also can move to primary importance (or to some other positions) from the second position.Such as, be transferred and/or be received from skin (such as, using mass transfer parts) at fluid after, launching actuator can move, and this can make mass transfer parts move away the contact with skin.Launching actuator can use any appropriate technology (comprising those technology above-described) to move to primary importance from the second position, and is used for making expansion actuator can be same or different from from the technology that the second position moves to primary importance making expansion actuator move to the technology of the second position from primary importance.

In some cases, skin can be inhaled to mass transfer parts by supporting construction.Such as, in one group of embodiment, this device can comprise vacuum interface or region.This interface or region can be connected with vacuum source (outside of this device and/or inside), and when a vacuum is applied, skin can be attracted to this device, such as so that with the mass transfer component contact of such as one or more pin or microneedle.

In some cases, this device comprises and can apply the interface of vacuum to skin.This interface can be such as suction cup or circular bowl, and this suction cup or circular bowl are placed on the surface of skin, and vacuum is applied to this interface to produce vacuum.In one group of embodiment, as discussed here, this interface is a part for supporting construction.This interface can be formed by any suitable material, such as, and the polymer, polyurethane, acrylonitrile-butadiene rubber, EPDM rubber, neoprene etc. of glass, rubber, such as silicones.In some cases, such as, use vacuum grease, Dormant oils, gelinite, hydrogel etc., the sealing (such as, reducing to leak) between this interface and skin can be improved.In some cases, interface can be relatively little, such as, has and be less than about 5cm, be less than about 4cm, be less than about 3cm, be less than about 2cm, be less than about 1cm, be less than about 5mm, be less than about 4mm, be less than about 3mm, be less than about 2mm, or be less than the diameter of about 1mm.This interface can be circular, although other shape is also possible, such as, and square, star (have 5,6,7,8,9,10,11 etc. are most advanced and sophisticated), tear-drop shaped, avette, rectangle etc.In some cases, can use non-circular shape, this is because high-energy is most advanced and sophisticated, and the tip of such as this shape or bight can be improved or accelerate foam and be formed.The non-limitative example of this shape is illustrated in figure 6.Also other non-circular shape in addition can be used in other embodiments.

In one group of embodiment, this device comprises expansion actuator, mass transfer parts can be driven in skin by this expansion actuator, such as, make this device can receive fluid from the skin of experimenter and/or below this skin, and/or make mass transfer parts can transportation of substances to experimenter, such as transportation of substances is to the skin of experimenter and/or to the position below this skin.Launching actuator can be a kind of structure, this structure can use without auxiliary power (such as, promoting this structure by people) or other power (such as, power of electricity applying, mechanical interaction etc.) and be out of shape, but its original shapes can be recovered after this power is removed or reduces at least in part.Such as, this structure can spontaneously recover its original shapes, maybe may need some effects (such as, heating) by this structure recovery to its original shapes.In one group of embodiment, launching that actuator can comprise can the flexibility of movement is recessed into component or can be reversibly out of shape between the first structure with the second structure structure.In some cases, launch actuator to be formed by suitable elastomeric material.Such as, this structure can be formed by plastics, polymer, metal etc.In one group of embodiment, this structure can have shape that is recessed or that protrude.Such as, the edge of this structure make this structure outside " bending " to be formed recessed or to protrude shape under can be placed in compression stress.Promote people that is recessed or that protrude shape and can make this malformation, but after people stops promoting this structure, this structure can turn back to that it is recessed or protrude and formed at first, such as, as previously mentioned spontaneously or by other power.In some cases, this device can be bistable, that is, have two diverse locations, and this device is stable in these two diverse locations.

Launch actuator to be formed by any suitable material, such as, such as stainless metal (such as, 301, 301LN, 304, 304L, 304LN, 304H, 305, 312, 321, 321H, 316, 316L, 316LN, 316Ti, 317L, 409, 410, 430, 440A, 440B, 440C, 440F, 904L), carbon steel, spring steel, spring brass, phosphor bronze, beryllium copper, titanium, titanium alloy steel, chrome alum, nickel alloy steel (such as, Monel400, MonelK500, Inconel600, Inconel718, Inconelx750, etc.), polymer (such as, polrvinyl chloride, polypropylene, Merlon, etc.), composite or laminates are (such as, comprise glass fibre, carbon fiber, bamboo, Kevlar, etc.), or analog.Launch actuator and can have any shape and/or size.Such as, launch actuator and can have hemispherical shape (such as, as in the young sheet of pot) substantially, and be circular (not having lower limb), or this expansion actuator can have other shape, such as, rectangle, triangle (3 lower limb), square (4 lower limb), pentagon (5 lower limb), hexagon (6 lower limb), Aranea lower limb, starlike, cloverleaf pattern (has any amount of leaf, such as 2,3,4,5 etc.), etc.In certain embodiments, launch actuator and can have hole, nick or button in centre.Launch disk or wave-like that actuator also can have band sawtooth.In some cases, mass transfer parts can be arranged on and launch on actuator.But in other situation, mass transfer parts are arranged in the structure of separation, the structure of this separation is driven when expansion actuator moves or is activated.

In one group of embodiment, launching actuator is not plane, and have the part that can be in primary importance (" tilting " or the position before launching) or the second position (" release " or the position of launching), this primary importance and the second position are constructed by relative high-energy alternatively and are separated.In certain embodiments, the position before expansion can be in higher energy level than expanded position.In some cases, primary importance and the second position are stable (that is, this structure are bistable), although the conversion between primary importance and the second position needs this structure through unstable structure.

According to one group of embodiment, many devices as discussed here use various technology to carry and/or receive fluid, such as, insert object etc. combine with mass transfer parts, skin.Such as, as described above, one or more pin and/or microneedle, hygroscopic agent, cutter or other pierce through auxiliary system of element, electricity etc. and can be used in conjunction with the young sheet of pot or other device.Be described in the application that the other example of this technology here and/or is here incorporated to.Should be appreciated that usually, can carry in every way and/or receive fluid, and be used for carrying and/or coming into question from the application that the various system and methods that skin receives fluid are incorporated to below and/or here.In certain embodiments, such as, the surface being used for piercing through or changing skin comes into question with the technology of transporting fluid, such as, use the pin of such as hypodermic needle or microneedle, be applied to the chemical substance (such as, penetration enhancer) of skin, other technology of jet injector or all those technology as discussed below, etc.

Such as, in one embodiment, the pin of such as hypodermic needle may be used for conveyance fluid to skin and/or from skin reception fluid.Hypodermic needle is well-known to those skilled in the art, and commercially can obtain with a series of gauge.Such as, this pin can in 20-30 specification limit, or this pin can be 32 specifications, 33 specifications, 34 specifications etc.

If pin exists, this pin can be any suitable dimension and length, and can be solid or hollow.This pin can have any suitable cross section (such as, perpendicular to penetration direction), such as, circular, foursquare, avette, oval, rectangle, round rectangle, leg-of-mutton, polygonal, hexagonal, irregular etc.Such as, this pin can have the length being less than about 5mm, being less than about 4mm, being less than about 3mm, being less than about 2mm, being less than about 1mm, being less than about 800 microns, being less than 600 microns, being less than 500 microns, being less than 400 microns, being less than about 300 microns, being less than about 200 microns, being less than about 175 microns, being less than about 150 microns, being less than about 125 microns, being less than about 100 microns, being less than about 75 microns, being less than about 50 microns etc.This pin also can have the cross-sectional dimension being less than about 5mm, being less than about 4mm, being less than about 3mm, being less than about 2mm, being less than about 1mm, being less than about 800 microns, being less than 600 microns, being less than 500 microns, being less than 400 microns, being less than about 300 microns, being less than about 200 microns, being less than about 175 microns, being less than about 150 microns, being less than about 125 microns, being less than about 100 microns, being less than about 75 microns, being less than about 50 microns etc.Such as, in one embodiment, this pin can have the rectangular cross section of the size of 175 microns × 50 microns.In one group of embodiment, this pin can have the length of at least approximately 2:1, at least approximately 3:1, at least approximately 4:1, at least 5:1, at least approximately 7:1, at least approximately 10:1, at least approximately 15:1, at least approximately 20:1, at least approximately 25:1, at least approximately 30:1 etc. to the aspect ratio of cross-sectional dimension.

In one embodiment, this pin is microneedle.Such as, the U.S. Patent No. 6 being entitled as " MicroneedleDevicesandMethodsofManufactureandUseThereof " of the people such as the Allen that such as on January 1st, 2002 promulgates, 334, the microneedle of those microneedle disclosed in 856 may be used for conveyance fluid or other material receives fluid or other material to experimenter and/or from experimenter.Microneedle can be hollow or solid, and can be formed by any suitable material, such as, and metal, pottery, quasiconductor, Organic substance, polymer and/or composite.Example includes but not limited to pharmaceutical grade rustless steel, titanium, nickel, ferrum, gold, stannum, chromium, copper, the alloy of these or other metal, silicon, silicon dioxide and polymer, polymer comprises such as lactic acid and polylactic-co-glycolic acid, polyglycolide, Poly(D,L-lactide-co-glycolide, and hands over the copolymer of caprolactone, Merlon, polymethylacrylic acid, polyvinyl acetate ethylene, politef, polymethyl methacrylate, polyacrylic acid or polyester with Polyethylene Glycol, condensing model, poe, polyurethane, poly-butanoic acid, poly-valeric acid, poly-third.

In some cases, more than one microneedle can be used.Such as, the array of microneedle can be used, and microneedle can be arranged in the array with any suitable constructions (such as, periodically, random, etc.).In some cases, this array can have the microneedle of 3 or more, 4 or more, 5 or more, 6 or more, 10 or more, 15 or more, 20 or more, 35 or more, 50 or more, 100 or more or other suitable quantity any.In certain embodiments, this device can have at least 3 but be no more than 5 pins or microneedle (or other skin inserts object), at least 6 but be no more than 10 pins or microneedle or at least 11 but be no more than 20 pins or microneedle.Typically, microneedle will have the mean cross sectional size (such as, diameter) being less than about 1 micron.Should be appreciated that as discussed here to " pin " or " microneedle " mention by means of only example mode and conveniently to express, and in other embodiments, in any description here, more than one pin and/or microneedle can be there is.

Those skilled in the art can arrange pin in order to these objects relative to skin, in one embodiment, comprise and with the angle being different from 90 °, pin is incorporated in skin relative to the surface of skin, that is, in an inclined manner pin is incorporated in skin to limit the degree of depth penetrated.But in another embodiment, pin can enter skin with approximate 90 °.

Pin or microneedle can have any appropriate length, and in some cases, this length can depend on application.Such as, the pin being designed to only penetrate epidermis can be shorter than the pin being designed to also penetrate corium or extend below corium or skin.In certain embodiments, microneedle can have and is no more than about 3mm, be no more than about 2mm, be no more than about 1.75mm, be no more than about 1.5mm, be no more than about 1.25mm, be no more than about 1mm, be no more than about 900 microns, be no more than about 800 microns, be no more than about 750 microns, be no more than about 600 microns, be no more than about 500 microns, be no more than about 400 microns, be no more than about 300 microns, be no more than about 200 microns, be no more than about 175 microns, be no more than about 150 microns, be no more than about 125 microns, be no more than about 100 microns, be no more than about 75 microns, be no more than about 50 microns etc. to the maximum penetration in skin.In certain embodiments, pin or microneedle can be selected to and have at least about 50 microns, at least about 100 microns, at least about 300 microns, at least about 500 microns, the maximum insertion depth of at least approximately 1mm, at least approximately 2mm, at least approximately 3mm etc.

In one group of embodiment, pin (or microneedle) can be coated.Such as, pin can be coated with the material be transferred when pin is inserted in skin.Such as, this coating can comprise heparin, anticoagulant, anti-inflammatory compound, analgesic, hydryllin compound or vasodilation with the skin flow of assist blood from experimenter.This coating can comprise medicine or all as described herein those other therapeutic agents.This medicine or other therapeutic agent can be for local (such as, the pin of coating or microneedle be applied to region on it or it near) medicine carried or therapeutic agent, and/or this medicine or other therapeutic agent can be the medicine carried of the system be intended in subject or other therapeutic agent.

By using dip-coating or spraying or other appropriate technology, at least some skin inserts object can at least in part by the coating substance of such as medicine, analgesic or medicament.Therefore, this material can skin or other experimenter position or in by substance dissolves or be otherwise transported to skin with mass transfer isolation of components.Alternatively, this material can be transferred after mass transfer parts penetrate experimenter, such as, to be similar to the mode of hypodermic needle.Such as, the skin of mass transfer parts inserts object and can be inserted in skin, and material can be pumped or push through skin inserts the hole of object, groove or other passage (such as, passing through gases at high pressure).

Medicine can be have treatment, prevention or any composition of diagnostic properties in vivo, such as, when being applied to the animal comprising mammal (such as the mankind).Medicine may be used for Local treatment or for region or systematic treating.This medicine can be or comprise peptide, protein, carbohydrate (comprise monosaccharide, oligosaccharide, and polysaccharide), nucleoprotein, mucin, lipoprotein, glycoprotein, nucleic acid molecules (comprise any type of DNA, such as cDNA, RNA, or its fragment, oligonucleotide, and gene), nucleotide, nucleoside, lipid, biological activity organic or inorganic molecule or its combination.The suitable example treating and/or preventing activating agent comprises anti-infective, analgesic, anti-inflammatory agent, steroid, decongestant, neural activity agent, anesthetics and tranquilizer.The example of suitable diagnostic agent comprises radiosiotope and radiopaque reagent, metal, gas, comprises the label of chromatograph, fluorescence or enzyme label.

The example of biologically active polypeptide or protein includes but not limited to glucagon, such as GLP-1, the glucagon-like peptide of GLP-2 or other GLP analog, the derivant of glucagon-like peptide or agonist, such as maliciously clearly outer secrete peptide-3 and poison is clear secretes peptide-4 outward, derivant, the poison of agonist and analog thereof is clear secretes peptide outward, vasoactive intestinal peptide (VIP), immunoglobulins, antibody, cytokine (such as, lymphokines, monokine, chemotactic factor), interleukin, macrophage activating factor, interferon, erythropoietin, nuclease, tumor necrosis factor, colony stimulating factor (such as, G-CSF), insulin, enzyme (such as, superoxide dismutase, plasminogen activator, etc.), tumor-inhibiting factor, haemproteins, hormone and hormone analogues and agonist (such as, follicle stimulating hormone, growth hormone, thyroliberin and luteinizing hormone releasing hormone (LHRH)), vaccine (such as, tumor, antibacterial and virus antigen), antigen, blooc coagulation factor, somatomedin (NGF and EGF), Gastrin., GRH, such as alexin, enkephalin, bradykinin, the antibacterial peptide of calcitonin and mutein, all aforesaid analog, clip, delete and alternative variations and pharmaceutically acceptable salt.Suitable analgesic includes but not limited to lignocaine, marcaine and tetracaine.Suitable steroid includes but not limited to corticosterone, betamethasone, budesonide and fluticasone.

In one group of embodiment, pin or microneedle may be used for conducting drugs in the skin of experimenter.Pin or microneedle can be coated at least in part, and this coating can comprise medicine or other therapeutic agent, such as described here those.Such as, in one group of embodiment, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or substantially all pins or microneedle can be coated, and one or more than one pin or microneedle can be coated in device as discussed here.Such as, at least about 25%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90% or substantially all devices in pin or microneedle can comprise coating.

When not wishing by any theory constraint, can believe, at least in some cases, longer pin or microneedle may be useful for the conveying of medicine or other therapeutic agent.Such as, having the larger pin to the penetration depth in skin can be used for medicine or other therapeutic agent to be transported to deeper in skin (such as, the capillary tube of in closer skin or below), this minimum medication systematically can allow starting faster of effect of drugs by the distance needing before to advance.In addition, larger penetration depth can be used for carrying relatively large medicine.Relative to shorter pin (such as, same diameter), longer pin can have the more multilist area in experimenter's interior exposed, and the surface area increased can allow the medicine that more multicoat comprises to expose in skin.Therefore, such as, each pin or the microneedle that enter skin can carry relatively large medicine.

Therefore, in certain embodiments, such as, relatively long pin or microneedle may be used for medicine or other therapeutic agent to be transported in skin.Such as, in certain embodiments, the pin in this device or the average length of microneedle can be at least about 200 microns, at least about 300 microns, at least about 400 microns, at least about 500 microns, at least about 600 microns, at least about 750 microns, at least about 800 microns, at least about 900 microns, at least about 1,000 micron, at least about 1,200 microns, at least about 1,500 microns, at least about 1,700 microns, or at least about 2,000 micron.

Any technology of multiple appropriate technology may be used for coating pin or microneedle.Such as, by pin or microneedle being exposed to the liquid comprising and want coated material thereon, pin or microneedle can be applied.Such as, pin or microneedle can be immersed in liquid, liquid can injected or atomization on pin or microneedle, electric field may be used for charged liquid to be attracted in pin or microneedle, etc.

In one embodiment, such as, by handling the plunger on syringe, manually carry and/or receive fluid.In another embodiment, such as, use piston pump or analog, mechanically or automatically can carry and/or receive fluid from skin.Fluid also can use vacuum (all those vacuum as discussed here) to be received in this device.Such as, vacuum can be applied to the conduit of the such as pin be communicated with body fluid fluid to draw this fluid at least partially from skin.In another embodiment, capillarity is used to receive fluid (such as, use microfluidic channel or have the hypodermic needle of interior diameter narrow suitably).In another embodiment, pressure can be applied and leave pin to force fluid.

In certain embodiments, material is transported to experimenter from device.When pin or other skin insert object scribble medicine or other material, this device can by with the needle-penetration skin of coating by medicine or substance use to experimenter.This material can at skin or other experimenter position by substance dissolves or be otherwise transported to skin or face under the skin with mass transfer isolation of components.This device can cause or not cause fluid to discharge from experimenter.In some cases, not to be received in this device from the fluid of experimenter and not need vacuum source.And, in some cases, this device can additionally or alternatively conveyance fluid medicine or other flowing material to experimenter.Flowing material can be transported to below skin or skin by hollow pin, fluid is transferred to experimenter from this device by this hollow pin.

As another example, pressure fluid may be used for conveyance fluid or other material in skin, such as, uses jet injector or " needleless injector ".Typically, this device produces the high pressure " jet " material being driven into liquid in skin or powder (such as, the bio-compatible liquid of such as saline), and such as can control penetration depth by the pressure of control jet.This pressure can from any suitable source, such as, and Standard Cylinder or inflator.In the U.S. Patent No. 4 being entitled as " HydraulicallyPoweredHypodermicInjectorwithAdaptersforRed ucingandIncreasingFluidInjectionForce " of the Ismach that on August 1st, 1978 promulgates, 103, the non-limitative example of this device can be seen in 684.

In certain embodiments, can use be applied to skin surface or close to skin hygroscopic agent receive liquid.Such as, device as described herein can comprise hygroscopic agent.In some cases, pressure can be applied to be driven in skin by hygroscopic agent.Hygroscopic agent typically can absorb water from surrounding, such as, by absorbing or adsorbing.The non-limitative example of hygroscopic agent comprises sugar, honey, glycerol, ethanol, methanol, sulphuric acid, methamphetamine, iodine, many chlorides and hydroxide salt and various other materials.Other example includes but not limited to zinc chloride, calcium chloride, potassium hydroxide or sodium hydroxide.In some cases, suitable hygroscopic agent can be selected based on its physics or reaction property (such as, for inertia or the biocompatibility of the skin of experimenter) according to application.

In certain embodiments, this device can comprise the cutter that can cut or pierce through the surface of skin.This cutter can comprise any mechanism that can produce path, can be carried and/or receive fluid from skin by this path.Such as, this cutter can comprise hypodermic needle, blade (such as, little cutter blade, indented knife etc.), pierce through element (such as, lancet or solid or hollow pin) or analog, they can be applied to skin to produce suitable conduit to carry and/or to receive fluid from skin.In one embodiment, cutter is for generation of this path and be removed, and then by this delivery pathways and/or can receive fluid.In another embodiment, the appropriate location in skin stayed by cutter, and by the conduit conveying in cutter and/or can receive fluid.

In certain embodiments, electric charge can be used to receive fluid.Such as, reverse ion osmosis can be used.When not wishing by any theory constraint, reverse ion osmosis uses little electric current to drive the charged and compound of high polarity to cross over skin.Because skin is electronegative with physiological pH, it serves as cationic permselective membrane, and counter ion causes electric osmose solvent stream through skin, and this electric osmose solvent stream can transport neutral molecule along anode to cathode direction.Other place as here describes, and can analyze the composition in solvent stream.In some cases, reverse ion osmosis equipment can comprise respectively with anode unit and the cathode electrode unit of contact skin.Anode unit can be filled with water buffer solution (that is, water TRIS buffer) and the electrolyte (that is, sodium chloride) that such as pH is greater than 4.Cathode electrode unit can be filled with water buffer.As an example, the first electrode (such as, anode) can be inserted in anode unit, and the second electrode (such as, negative electrode) can be inserted in cathode electrode unit.In certain embodiments, electrode not with direct skin contact.

Electric current can be applied permeate to cause reverse ion, therefore receive fluid from skin.The electric current applied can such as be greater than 0.01mA, is greater than 0.3mA, is greater than 0.1mA, is greater than 0.3mA, is greater than 0.5mA or is greater than 1mA.Should be appreciated that and also can use these extraneous electric currents.The time period of this continuing current flow setting can be applied.Such as, this continuing current flow can be applied be greater than 30 seconds, be greater than 1 minute, be greater than 5 minutes, be greater than 30 minutes, be greater than 1 hour, be greater than 2 hours or be greater than 5 hours.Should be appreciated that and also can use these extraneous time.

In one group of embodiment, this device can comprise the mass transfer parts of the form of the equipment for melting skin.When not wishing by any theory constraint, can believe, melting to comprise and removing cuticular minute fragments (that is, melting formation micropore), therefore allowing close to body fluid.In some cases, heat, radio frequency and/or laser energy may be used for melting.In some cases, heating element heater can be used to apply heating ablation.Can use and the frequency of heating water and/or tissue and energy can perform radio-frequency (RF) ablation.Laser also may be used for irradiating position on skin to remove a part.In certain embodiments, the precipitous thermograde existence that heat makes to be substantially perpendicular to the surface of skin can be applied in a pulsed fashion.Such as, the constant temperature that can apply at least 100 DEG C, at least 200 DEG C, at least 300 DEG C or at least 400 DEG C is less than 1 second, is less than 0.1 second, is less than 0.01 second, is less than 0.005 second or is less than 0.001 second.

In certain embodiments, this device can comprise the mass transfer parts of the form of the mechanism for obtaining Solid Tissue Samples.Such as, can pass through such as to swipe skin or cut out a part of method to obtain Solid Tissue Samples.Scraping can comprise reciprocating action, and instrument is swiped along the surface of skin in two or more directions thus.Scraping also can be implemented by spinning movement, such as, this spinning movement be parallel to skin surface and along a direction (that is, by cylinder) or the surface being parallel to skin and in a circular manner (that is, by borehole apparatus).Cutting mechanism can comprise the blade can making one or more otch and the mechanism being used for removing part tissue (that is, by drawing or mechanically picking up), or can use pincer mechanism to cut out part tissue.Cutting mechanism also can be worked by coring action.Such as, hollow cylinder device can thrust in skin and the cylindrical core of tissue can be removed.Solid sample can be analyzed directly or can be liquefied before analysis.Liquefaction can comprise the process by organic solvent, enzymatic solution, surfactant etc.

In certain embodiments, this device also can comprise vacuum source.In some cases, this vacuum source provides the vacuum source in this device for oneself, that is, during this device is used for receiving blood from skin, this device does not need to be connected to external vacuum source (such as, device vacuum system (housevacuum)).Such as, in one group of embodiment, vacuum source can comprise vacuum chamber, before blood (or other fluid) is received in this device, the pressure of this vacuum chamber is less than atmospheric pressure, namely, this vacuum chamber is in " negative pressure " (that is, be negative relative to atmospheric pressure) or " vacuum pressure " (or only having " vacuum ").Such as, vacuum pressure in this vacuum chamber can be at least about 50mmHg, at least approximately 100mmHg, at least approximately 150mmHg, at least approximately 200mmHg, at least approximately 250mmHg, at least about 300mmHg, at least approximately 350mmHg, at least approximately 400mmHg, at least approximately 450mmHg, at least approximately 500mmHg, at least 550mmHg, at least 600mmHg, at least 650mmHg, at least approximately 700mmHg or at least approximately 750mmHg, namely lower than atmospheric pressure.But, in other embodiments, should be appreciated that and other pressure and/or distinct methods can be used to may be used for producing other pressure (being greater than or less than atmospheric pressure).As non-limitative example, external vacuum or machinery can be used as vacuum source; Discuss various other example here in detail.

As special non-limitative example, in one embodiment, device can when not having external power supply and/or vacuum source for receiving fluid.The example of this device comprises transdermal patches, band, adhesive tape, binder or analog.Such as, transdermal patches can with the contact skin of experimenter, and vacuum can be produced by the alteration of form of the part of transdermal patches or other device (such as, using shape-memory polymer), and this vacuum may be used for conveying and/or receives fluid from skin.As special example, shape-memory polymer can be shaped as in the first temperature (such as, room temperature) under be flat, but in the second temperature (such as, body temperature) under be bending, and when being applied to skin, shape-memory polymer from flat alteration of form to bending shape, therefore can produce vacuum.As another example, machinery may be used for producing vacuum.Such as, the foam of spring, coil, expansion (such as, from compression state), shape-memory polymer, shape memory metal or analog can with compression d/d when being applied to experimenter or winding state be stored, then (such as, untie, decompress etc.) is released mechanically to produce vacuum.

Therefore, in some cases, this device " encapsulates " in advance suitable vacuum source (vacuum chamber of such as, finding time in advance); Such as, in one embodiment, this device can be applied to skin and be activated in some manner produce and/or access vacuum source.In another example, chemical reaction may be used for producing vacuum, and such as, produce the reaction of gas, this chemical reaction may be used for providing mechanical force to produce vacuum.In another example, the parts of this device can produce vacuum when not having mechanical force.In another example, this device can comprise provides vacuum actuator for oneself, such as, and chemical reactant, deformable structure, spring, piston etc.

In one group of embodiment, this device can produce pressure differential (such as, vacuum).Pressure differential can be produced by pressure regulator.As used herein, " pressure regulator " is Pressure Control Unit or the system that can produce pressure differential between two or more positions.According to various embodiment of the present invention as discussed here, pressure differential at least should be enough to the movement promoting fluid or other material, and the absolute pressure at two or more positions is unessential, as long as their difference is suitable, and their absolute value is rational for object discussed here.Such as, relative to the lower pressure (atmospheric pressure or some other pressure) at another position, pressure regulator can produce the pressure higher than atmospheric pressure in a position, and the difference wherein between pressure is enough to promote according to fluid of the present invention.In another example, the pressure lower than atmospheric pressure (vacuum) that this actuator or controller will relate in a position, with the elevated pressures (atmospheric pressure or different pressures) at another position, the difference wherein between pressure is enough to promote according to fluid of the present invention." vacuum " or " pressure " is used here in whatsoever situation, in conjunction with pressure regulator of the present invention or pressure differential, be to be understood that, as the skilled person will appreciate, also contrary situation can be implemented, that is, vacuum chamber can be replaced with pressure chamber in many cases, to produce the pressure differential being suitable for the movement promoting fluid or other material.

Pressure regulator can be external vacuum source (such as, laboratory, clinic, hospital etc. device vacuum system pipeline or external vacuum pump), machinery, vacuum chamber, the vacuum chamber that encapsulates in advance etc.In some cases, manually can producing vacuum, such as, by handling syringe pump, plunger etc., or mechanically or automatically can produce low pressure, such as, use piston pump, syringe, round, Venturi tube, manpower (mouth) suction etc.Can vacuum chamber be used in certain embodiments, wherein this device comprise such as vacuum leave maybe can produce region (such as, variable volume chambers, its volume change will realize vacuum or pressure).Vacuum chamber can comprise (namely encapsulating in advance) room or the region of finding time in advance and/or provide actuator for oneself.

" providing " vacuum (or pressure) adjusting device for oneself is associate (such as with this device, on the apparatus or interior) device, such as, limit the device of the ingredient of this device, or structure and be arranged to can be connected to especially special device (that is, be free of attachment to external vacuum source, such as hospital, clinic, or the device vacuum pipeline of laboratory or be applicable to the vacuum pump of very common purposes) with the separating component of mineralization pressure difference.In certain embodiments, provide vacuum source for oneself and can activated to produce vacuum in some manner in this device.Such as, provide for oneself vacuum source can comprise piston, syringe, all if in this device the machinery of vacuum vacuum pump and/or chemical substance or other reactant, this chemical substance or other reactant can react increase or reduce pressure, this pressure the machinery driven by this reaction or other device auxiliary under, the pressure differential associated with pressure regulator can be formed.Chemical reaction also can by or not by based on chemical reaction self pressure change driving device activate.Provide vacuum source for oneself and also can comprise expandable foam, shape-memory material etc.

A class of the present invention is provided vacuum or pressure regulator for oneself and is comprised and provide auxiliary governor for oneself.These are actuators, and this actuator is (such as, promotion button, or the self actuating when such as removing from encapsulation or pushed away on skin by device) when activating, and form the vacuum or pressure that associate with this device, wherein the power of pressurization or evacuated chamber is different from actuation force.The example providing auxiliary governor for oneself comprises by the room activating the spring, the release of shape-memory material or expandable material when activating, the startup etc. of chemical reaction drives when activating the expansion that trigger and find time.

Of the present inventionly another kind ofly provide vacuum for oneself or pressure regulator is the device that need not be packaged with pressure or vacuum in advance, but this device can such as be pressurizeed in hospital or clinic by experimenter, health professional or find time before the use, such as, by the room of this device is connected to vacuum or pressure source.Such as, experimenter or another people can activate this device to produce pressure or vacuum in this device, such as, just before the use of this device.

This vacuum or pressure regulator can be that " in advance encapsulate " pressure in the apparatus or vacuum chamber be (namely when deployed, this device can be provided to use in order to experimenter or practitioner, on the apparatus or in there is the region of finding time, and without any need for actuating to form initial vacuum).The pressure encapsulated in advance or vacuum chamber actuator can be the regions (relative to atmospheric pressure) of finding time in some moment such as during fabrication and/or before the moment that it is used by experimenter or practitioner.Such as, evacuated chamber during fabrication or after the fabrication but before this device is transported to user (such as, clinician or experimenter).Such as, in certain embodiments, this device comprises vacuum chamber, this vacuum chamber has subatmospheric at least approximately 50mmHg, at least approximately 100mmHg, at least approximately 150mmHg, at least approximately 200mmHg, at least approximately 250mmHg, at least approximately 300mmHg, at least approximately 350mmHg, at least approximately 400mmHg, at least approximately 450mmHg, at least approximately 500mmHg, at least approximately 550mmHg, at least approximately 600mmHg, at least approximately 650mmHg, at least approximately 700mmHg, or the vacuum of at least about 750mmHg.

In one group of embodiment, device of the present invention can not have external impetus and/or vacuum source.In some cases, this device " loads " in advance suitable vacuum source; Such as, in one embodiment, this device can be applied to skin and be activated in some manner produce and/or access vacuum source.As an example, device of the present invention can with the contact skin of experimenter, and vacuum can produce (such as by the alteration of form of a part for this device, use shape-memory polymer), or this device can comprise one or more sealing provide vacuum chamber for oneself, wherein sealing member is pierced to produce vacuum in some manner.Such as, when puncture through seal part, vacuum chamber can be communicated with pin fluid, and this may be used for skin is moved towards this device, receives fluid from skin, etc.

As another example, shape-memory polymer can be shaped as in the first temperature (such as, room temperature) under be flat, but in the second temperature (such as, body temperature) under be bending, and when being applied to skin, shape-memory polymer from flat alteration of form to bending shape, therefore can produce vacuum.As another example, machinery may be used for producing vacuum.Such as, the foam of spring, coil, expansion (such as, from compression state), shape-memory polymer, shape memory metal or analog can with compression d/d when being applied to experimenter or winding state be stored, then be released (such as, untie, decompress etc.) mechanically to produce vacuum.The non-limitative example of shape-memory polymer and metal comprises Nitinol, the synthetic of oligomeric (6-caprolactone) two and crystallizable oligomeric (ρ-dioxanone) glycol, or the synthetic of oligomeric (6-caprolactone) dimethylacrylate and n-butyl acrylate.

In another example, chemical reaction may be used for producing vacuum, and such as, produce the reaction of gas, this chemical reaction may be used for providing mechanical force to produce vacuum.In certain embodiments, this device just may be used for automatically producing vacuum once be activated, and does not need any external control of user.

In one group of embodiment, this device comprises vacuum chamber, and this vacuum chamber is also used as locker room blood or other fluid to be received in this device from experimenter.Such as, by or the blood that receives from experimenter via mass transfer parts can enter vacuum chamber due to the negative pressure (that is, because the internal pressure of this room is less than atmospheric pressure) of vacuum chamber, and to store alternatively in a vacuum chamber to use later.Non-limitative example shown in Fig. 3.In this drawing, device 600 comprises vacuum chamber 610, and it can be such as one or more microneedle that this vacuum chamber is connected to these mass transfer parts of mass transfer parts 620().When starting vacuum chamber 610 (such as, using actuator 660 as discussed below), vacuum chamber 610 can be made to be communicated with mass transfer parts 620 fluid.Therefore mass transfer parts 620 can cause negative pressure to be applied to the skin of experimenter, such as, due to the internal pressure in vacuum chamber 610.Therefore the fluid (such as, blood) leaving skin via mass transfer parts 620 can be drawn onto in this device and in vacuum chamber 610, such as, by conduit 612.The fluid collected by this device subsequently can be analyzed or remove to analyze, store etc. from this device in this device.

But in another group embodiment, this device can comprise vacuum chamber and locker room (such as, for storing such as from the room of the fluid of the blood of experimenter) of separation.Vacuum chamber can be communicated with by fluid with locker room, and can have any suitably-arranged.In certain embodiments, the vacuum of vacuum chamber can at least in part for receiving fluid from skin, and this fluid is introduced in locker room subsequently, such as, so that with post analysis or use, such as, as discussed below.Such as, blood can be received in this device, flows to vacuum chamber, but this fluid can be prevented from entering vacuum chamber.Such as, in certain embodiments, gas-permeable can be used but the impermeable material of liquid of such as blood.Such as, this material can be film (such as hydrophilic or hydrophobic film), and this film has suitable porosity, loose structure, porous ceramics frit, soluble interface (such as, being formed by salt or polymer etc.) etc.

In certain embodiments, mass transfer parts can be fastened to and launch on actuator.In some cases, launch actuator and mass transfer parts can be guided to skin, and in some cases, mass transfer parts are inserted in skin.Such as, can pass through piston, screw rod, mechanical linkages etc. mechanically, (such as, by servo, this servo may be computer-controlled), pneumatically moving matter transmission part electrically.As mentioned, in certain embodiments, blood or other body fluid can be stored in this device to use and/or to analyze later.Such as, this device can be connected to suitable external equipment, this external equipment can analyze a part (such as, comprising this fluid) for this device, and/or this external equipment can remove at least some of blood or other fluid so that subsequent analysis and/or storage from this device.Such as, but in some cases, at least some analysis can be performed by this device self, uses one or more sensor comprised in this device etc.

As mentioned, in one group of embodiment, device of the present invention as discussed here can be transported to another place to analyze.In some cases, this device can comprise anticoagulant or stabilizing agent, and this anticoagulant or stabilizing agent are comprised in this device, such as, in the locker room of fluid.Therefore, such as, can be transported to the room (such as, locker room) in this device from the fluid of the such as blood of skin reception, then a part (such as, module) for this device or this device can be transported to another place to analyze.Any type of transport can be used, such as, by postal delivery.

The non-limitative example of various device of the present invention shown in Fig. 1.In figure ia, when on the skin that this device is placed on experimenter, device 90 is for receiving fluid from experimenter.As discussed here, device 90 comprises sensor 95 and mass transfer parts 92, such as, and pin, microneedle etc.What be communicated with mass transfer parts 92 fluid by fluid passage 99 is sense room 97.In one embodiment, sensing room 97 can comprise the reagent of such as particle, enzyme, dyestuff etc., to analyze the body fluid of such as interstitial fluid or blood.In some cases, mass transfer parts 92 can be used to receive fluid by vacuum, what comprise in this vacuum such as device 90 provides vacuum for oneself.Alternatively, device 90 also comprises display device 94 and the electronic equipment 93 associated, battery or other power supply etc., and this display device may be used for showing the sensor reading obtained by sensor 95.In addition, device 90 also can comprise memorizer 98 alternatively, be used for the transmitter etc. of the Signal transmissions of indication sensor 95 to receptor.

In the example illustrated in figure ia, device 90 can comprise the vacuum source (not shown) provided for oneself in device 90, although in other embodiments, vacuum source can be outside at device 90.(as discussed here, in other situation other, other system may be used for conveying and/or receives fluid from skin.) in one embodiment, after on the skin being placed on experimenter, such as, when being exposed to vacuum source, skin can by be upwards drawn onto comprise depression fluid transport device 92 in.Path to vacuum source can be controlled by any appropriate method, such as, by puncture through seal part or barrier film; By opening valve or mobile gate, etc.Such as, when starting drive 90 (such as, by experimenter, remotely, automatically etc.), vacuum source can be made to be communicated with this depression fluid skin is drawn onto in this depression due to vacuum.The skin be drawn onto in depression can insert object (such as, solid or hollow pin) with skin and contact, and this skin inserts object and can pierce through skin in some cases and allow fluid to be transported to skin and/or receive fluid from skin.In another embodiment, skin inserts object and can activated and move down to contact skin, and retracts alternatively after usage.

Another non-limitative example of device is illustrated in fig. ib.This illustrates the device that can be used for transporting fluid into experimenter.As discussed here, in this drawing, device 90 comprises mass transfer parts 92, and such as, these mass transfer parts comprise pin, microneedle etc.What be communicated with mass transfer parts 92 fluid by fluid passage 99 is room 97, and this room can comprise the medicine or other reagent that will be transported to experimenter.In some cases, can carry out conveyance fluid by pressure controller, and/or use mass transfer parts 92 to receive fluid by vacuum, what comprise in this vacuum such as device 90 provides vacuum for oneself.Such as, when producing vacuum, skin can be picked up towards mass transfer parts 92, and mass transfer parts 92 can pierce through skin.Then, the fluid from room 97 can be transported in skin by fluid passage 99 and mass transfer parts 92.Alternatively, device 90 also comprises display device 94 and the electronic equipment 93 associated, battery or other power supply etc., and this display device may be used for the conveying of the fluid controlling to skin.In addition, device 90 can also comprise memorizer 98 alternatively, be used for the transmitter etc. of the Signal transmissions of indicating device 90 or fluid conveying to receptor.

The another non-limitative example of device of the present invention is illustrated in fig. 2.Fig. 2 A illustrates the view (lid is removed) of this device, and Fig. 2 B illustrates this device with cross sectional schematic.In fig. 2b, device 50 comprises the pin 52 be comprised in depression 55.Depend on embodiment, pin 52 can be solid or hollow.Device 50 also comprises provides vacuum chamber 60 for oneself, and this provides the core that vacuum chamber winding needle 52 and depression 55 are positioned at this device wherein for oneself.Passage 62 connects the vacuum chamber 60 and depression 55 that are separated by paper tinsel or film 67.Button 58 is also show in device 50.When being pushed, button 58 staves paper tinsel 67, is thus connected vacuum chamber 50 and depression 55, in depression 55, produces vacuum.Such as, vacuum may be used for skin to be drawn onto in depression 55, is preferably so that its contact pin 52 and pierces through surface, therefore acquiring the path of internal flow.Such as, by controlling the size of pin 52 and therefore controlling penetration depth, this fluid can be controlled.Such as, penetrate and can be limited to epidermis (such as, being used for collecting interstitial fluid), or be restricted to corium (such as, being used for collecting blood).In some cases, vacuum also may be used for being fixed on the surface of skin by device 50 at least in part, and/or receives fluid for auxiliary from skin.Such as, fluid at the flows by action of vacuum in passage 62, and can flow to sensor 61 alternatively, and such as, this sensor is used for detecting the analysis thing comprised in this fluid.Such as, sensor 61 can be deposited at analysis thing and produce color change in case, or otherwise produces detectable signal.

In some embodiments of the invention, other parts can be added to the example of the device shown in Fig. 2.As discussed in more detail here, such as, device 50 can comprise lid, display device, port, transmitter, the passage of sensor, such as microfluidic channel, room and/or various electronic equipment, such as, so as to control or monitor enter or the fluid transport of separating device 50 so that the analysis thing determining to be present in the fluid that is transferred and/or receive from skin is to determine the state of this device so that report or transmission are about this device and/or the information etc. analyzing thing.As another example, device 50 can comprise binding agent (such as on surface 54), so that this device is adhered to skin.

Another non-limitative example is illustrated with reference to figure 2C.In this example, device 500 comprises supporting construction 501 and the mass transfer parts 503 associated.Mass transfer parts 503 comprise multiple pin or microneedle 505, although other skin as discussed here also can be used to insert object or flowing activation members.What also illustrate in fig. 2 c is sensor 510, and this sensor is connected to the depression 508 comprising pin or microneedle 505 by passage 511.Room 513 can be provide vacuum chamber for oneself, and room 513 can be communicated with depression 508 fluids by passage 511, such as, when being controlled by controller or actuator (not shown).In this drawing, device 500 also comprises display device 525, and this display device is connected to sensor 510 by electrical connection 522.As the example of operative installations 500, when from skin draw fluid (such as, blood, interstitial fluid etc.), fluid can flow through passage 511 to be determined (such as, due to the effect of the vacuum from vacuum chamber 513) by sensor 510.In some cases, vacuum is used for such as being drawn onto in depression 508 by skin, be preferably so that its contact pin or microneedle 505 and the surface of piercing through skin to acquire the path of the fluid (such as, blood or interstitial fluid etc.) of experimenter inside.Such as, by controlling the size of pin 505 and therefore controlling penetration depth, this fluid can be controlled.Such as, penetrate and can be limited to epidermis (such as, being used for collecting interstitial fluid), or be restricted to corium (such as, being used for collecting blood).When determining fluid and/or existence or the analysis thing be present in this fluid under a cloud, microprocessor or other controller can show suitable signal in display device 525.As discussed below, display device is illustrated by means of only the mode of example in this drawing; In other embodiments, can not display device be there is, or other signal can be used, such as, light, abnormal smells from the patient, sound, sense of touch, the sense of taste etc.

In certain embodiments, this device can be electricity and/or the machinery that can be applied to the surface (such as, using binding agent or other technology, all those technology as described herein) that maybe can be fixed to skin.This binding agent can be permanent or temporary transient, and may be used for the surface this device being fixed to skin.This binding agent can be any suitable binding agent, such as, and pressure sensitive adhesive, contact adhesive, permanent adhesives, hydrogel, cyanoacrylate adhesive, glue, natural gum, PUR, epoxy resin or analog.In some cases, this binding agent is selected to biocompatible or hypoallergenic.

In another group embodiment, this device mechanically can be remained to skin, and such as, this device can comprise mechanical organ, and this mechanical organ is such as with, belt, bracelet, cord, frenulum, elastic webbing or analog.Such as, band can be worn on around this device this device to be remained on the appropriate location on the skin of experimenter.In another group of embodiment, the combination of these and/or other technology can be used.As a non-limitative example, this device can use binding agent and band to be fixed to arm or the lower limb of experimenter.

But, in other embodiments, this device can such as mechanically be inserted in skin at least partially.Such as, in one embodiment, as discussed here, this device can comprise cutter, the such as hypodermic needle of this cutter, blade, pierces through element (such as, solid or hollow pin) or analog.In some cases, this device can comprise the cutter that can cut or pierce through the surface of skin.This cutter can comprise any mechanism in the path of the fluid that can produce in skin, such as, and can conveyance fluid and/or from skin removing fluids by this path.Such as, this cutter can comprise hypodermic needle, blade, pierce through element (such as, solid or hollow pin) or analog, and they can be applied to skin to produce suitable conduit to receive fluid from skin.In one embodiment, cutter is for generation of this path and be removed, and then uses any appropriate technology removing fluids by this path.In another embodiment, the appropriate location in skin stayed by cutter, and can by the conduit draw fluid in cutter.

Any or all layout described herein can be arranged near experimenter, such as, on the skin of experimenter or near.The startup of this device can be performed in many ways.In one embodiment, device can be applied to experimenter and start (such as, promoted by user, depressed or pat) region of device, to inject pin or microneedle so that close to interstitial fluid.Identical or different to pat or pushing action can start vacuum source, one or more of the multiple valve of open and/or closed, etc.This device can be simple device, wherein it is applied to skin and automatically operates (wherein, such as be applied to skin close to interstitial fluid and interstitial fluid is drawn in analyzed area), or this device can be applied to skin and one pat or other startup can cause that fluid flows through, the administration of pin or microneedle, the opening of valve, the startup of vacuum or any combination.Repeat to promote or pat a position or optionally, sequentially and/or periodically start multiple switch by user, any amount of startup scheme can be performed.In another is arranged, the startup of pin or microneedle, inhale the generation of bubble, the open and/or closed of valve and for promoting that other technology of one or more of analysis can be performed electronically or with the alternate manner that experimenter or external control entity promote.Such as, device or sticking patch can be arranged near the skin of experimenter, and radio frequency, electromagnetism or other signal can provide to start pin, foam device, the valve of described device or any of other parts by neighbouring controller or source at a distance that any one chemical examination can be performed as you wish.

In certain embodiments, fluid can be transported to experimenter, and this fluid can comprise the material useful to conveying, such as, this material formed fluid at least partially, to be dissolved in fluid, by fluid bearings (such as, suspension or dispersion) etc.The example of suitable material includes but not limited to the particle of such as microgranule or nanoparticle, chemical substance, medicine or therapeutic agent, diagnostic agent, carrier or analog.

As used herein, term " fluid " is often referred to and tends to flowing and the material complying with the profile of its container.Typically, fluid is the material that can not stand static shear stress, and when applying shear stress, fluid experiences continuous print and permanent distortion.Fluid can have any appropriate viscosity of at least some flowing allowing fluid.The non-limitative example of fluid comprises liquids and gases, but also can comprise free-pouring solids, viscoelastic fluid etc.Such as, this fluid can comprise flowable substrate or gelinite, and this substrate or gelinite are such as formed by biodegradable and/or biocompatible material (such as polylactic acid, polyglycolic acid, PLGA etc.) or other similar material.

In some cases, past, at present and/or in the future situation that the fluid of experimenter or other material may be used for indicating experimenter is transported to.Therefore, can be present in situation in experimenter at present and/or do not exist at present but experimenter easily suffers or be in addition the situation of the danger that it increases by the situation of the experimenter determined.This situation can be medical conditions, and such as, diabetes or cancer, or other physiological situation, such as dehydration, pregnancy, illicit drug use etc.In one group of embodiment, this material can comprise diagnostic agent, such as, can determine the diagnostic agent of analysis thing in the experimenter analysis thing of mark of morbid state (such as, be).As special non-limitative example, the material being transported to the skin (such as, to corium or epidermis, to the aggregation zone of fluid, etc.) of experimenter can comprise particle, and this particle comprises the antibody of the mark that directed toward bacteria produces.

But in other situation, the material being transported to experimenter may be used for the situation determining experimenter outside.Such as, this material can comprise can identify the encirclement pathogen of experimenter or the reaction entity of other environmental aspect, such as, can identify the antibody of external pathological body (or pathogen mark).

According to an aspect of the present invention, this device has relatively little size.In certain embodiments, this device can be designed to appropriate size and makes it to be dressed by experimenter and/or to carry.Such as, this device can be provided for oneself, does not need electric wire, cable, pipe, outer structural element or other external support component.This device can be arranged on any correct position of experimenter, such as, on arm or lower limb, on back, on abdominal part etc.As mentioned, in certain embodiments, this device can use any appropriate technology (such as, using the mechanical organ of binding agent, such as band, belt, bracelet, cord, frenulum, elastic webbing etc.) be fixed or remain on the surface of skin.In some cases, this device can be arranged on experimenter and make experimenter can stroll about (such as, take a walk, take exercise, typewrite, write, drink water or have a meal, use bathroom etc.) when dressing this device.Such as, this device can have quality and/or size and make experimenter can dress this device to continue at least about 5 minutes, and continue the longer time period in some cases, such as, at least about 10 minutes, at least about 15 minutes, at least about 30 minutes, at least about 45 minutes, at least about 1 hour, at least about 3 hours, at least 5 hours, at least about 8 hours, at least about 1 day, at least about 2 days, at least about 4 days, at least about 1 week, at least about 2 weeks, at least about 4 weeks etc.

In certain embodiments, this device is relative light weight.Such as, this device can have and is no more than about 1kg, is no more than about 300g, is no more than about 150g, be no more than about 100g, be no more than about 50g, be no more than about 30g, be no more than about 25g, be no more than about 20g, be no more than about 10g, be no more than about 5g, or be no more than the weight of about 2g.Such as, in various embodiments, this device has about 2g and the quality approximately between 25g, about 2g and the quality approximately between 10g, 10g and the quality approximately between 50g, about 30g and the quality approximately between 150g, etc.

In some cases, this device can be relatively little.Such as, this device can be configured to and be arranged to relatively locate near skin.Therefore, such as, this device can have and is no more than about 25cm, be no more than about 10cm, be no more than about 7cm, be no more than about 5cm, be no more than about 3cm, be no more than about 2cm, be no more than about 1cm, be no more than about 8mm, be no more than about 5mm, be no more than about 3mm, be no more than about 2mm, be no more than about 1mm, or be no more than the maximum vertical size (extending from the skin of experimenter when this device is disposed on skin) of about 0.5mm.In some cases, this device can have about 0.5cm and approximately between 1cm, and about 2 and approximately between 3cm, about 2.5cm and approximately between 5cm, about 2cm and approximately between 7cm, about 0.5mm and maximum vertical size approximately between 7cm etc.

In another group embodiment, this device can have relatively little size.Such as, this device can have and is no more than about 25cm, is no more than about 10cm, is no more than about 7cm, be no more than about 5cm, be no more than about 3cm, be no more than about 2cm, or be no more than the maximum transverse size (such as, being parallel to skin) of about 1cm.In some cases, this device can have about 0.5cm and approximately between 1cm, and about 2 and approximately between 3cm, about 2.5cm and approximately between 5cm, about 2cm and maximum transverse size approximately between 7cm etc.

In other embodiments, the combination of these and/or other size is also possible.As non-limitative example, this device can have the maximum transverse size being no more than about 5cm, is no more than the maximum vertical size of about 1cm, and is no more than the quality of about 25g; Or this device can have the maximum transverse size being no more than about 5cm, be no more than the maximum vertical size of about 1cm, and be no more than the quality of about 25g; Etc..

Such as, by promoting button, depress switch, moving slider, rotation rotating disk etc., this device can be started.Experimenter and/or another people can starting drive activation members.In some cases, this device can by remote activation.Such as, healthcare provider can send electromagnetic signal (this electromagnetic signal is received by this device) to start this device, and this electromagnetic signal is wireless signal, radio signal etc. such as.

In one group of embodiment, this device can comprise the passage of such as microfluidic channel, and this passage may be used for fluid and/or other material to be transported in skin and/or from skin and receives fluid and/or other material.In some cases, microfluidic channel is communicated with mass transfer component fluidic, and these mass transfer parts are used for transporting fluid into skin and/or receiving fluid from skin.Such as, in one group of embodiment, this device can comprise hypodermic needle, and this hypodermic needle can be inserted in skin, and fluid can be transported in skin and/or by this pin by this pin and receive fluid from skin.This device also can comprise one or more microfluidic channel to comprise fluid to be transported to this pin (such as, source from fluid), and/or receive fluid from skin, such as, so as to be transported to the analysis room in this device, to storage so that with post analysis, etc.

In some cases, more than one room may reside in this device, and in some cases, some or all of room can such as by the passage of such as microfluidic channel.In various embodiments, depend on application, multiple room and/or passage may reside in this device.Such as, this device can comprise for sensing analyze thing room, be used for keep reagent room, be used for control temperature room, be used for controls pH or other situation room, be used for produce or compensator or trimmer pressure or vacuum room, be used for control or damper fluid flow room, mixing chamber etc.

Therefore, in one group of embodiment, this device can comprise microfluidic channel.As used herein, " microfluid ", " microcosmic ", " minute yardstick ", micro-prefix (such as, as in " microchannel ") etc. are often referred to width or diameter is less than about 1mm, and is less than element or the article of about 100 microns in some cases.In certain embodiments, the microfluidic channel that can substitute or combine for any embodiment discussed here uses comparatively major path.Such as, width or diameter can be used in some cases to be less than about 10mm, be less than about 9mm, be less than about 8mm, be less than about 7mm, be less than about 6mm, be less than about 5mm, be less than about 4mm, be less than about 3mm or be less than the passage of about 2mm.In some cases, this element or article comprise passage, and fluid can flow through this passage.In all embodiments, specified width, which width can be minimum widith (namely, width wherein as specified, at that position, these article can have larger width in different sizes), or Breadth Maximum is (namely, wherein, at that position, these article have not wider than the width of specified width, which width, but can have larger length).Therefore, such as, microfluidic channel can have and is less than about 1mm, is less than about 500 microns, is less than about 300 microns or be less than the mean cross sectional size (such as, perpendicular to the flow direction of the fluid in microfluidic channel) of about 100 microns.In some cases, microfluidic channel can have and is less than about 60 microns, is less than about 50 microns, is less than about 40 microns, is less than about 30 microns, is less than about 25 microns, is less than about 10 microns, is less than about 5 microns, is less than about 3 microns or be less than the average diameter of about 1 micron.

As used herein, " passage " mean the article (such as, substrate) of the flowing guiding to fluid at least in part upper or in feature.In some cases, this passage can be formed by single parts (such as, etching substrates or moulding unit) at least in part.This passage can have any shape of cross section, such as, and circular, avette, triangle, irregular, square or rectangle (there is any aspect ratio) etc., and can be capped or be uncovered (that is, leading to the external environment condition of surrounding this passage).In the embodiment that passage is completely covered, at least one part of passage can have totally enclosed cross section, and/or whole passage can be except its whole length of its entrance and exit outer is complete totally enclosed.

Passage can have any aspect ratio, such as, and at least approximately aspect ratio (length is to mean cross sectional size) of 2:1, more typically at least about 3:1, at least approximately 5:1, at least approximately 10:1 etc.As used herein, " cross sectional dimensions " about fluid or microfluidic channel is measured along the direction of the fluid flowing be substantially perpendicular in passage.Passage will comprise the characteristic of control promoting convection cell transport usually, such as, and architectural characteristic and/or physics or chemical characteristic (hydrophobicity is to hydrophilic) and/or other characteristic of power (such as, tolerance) can be applied on fluid.Fluid in passage can partially or even wholly fill this passage.In some cases, this fluid can be kept in some manner or be limited in a part for passage or passage, such as, use surface tension (such as, make fluid such as recessed or protrude meniscus meniscus in be maintained in passage).In article or substrate, some (or whole) passages can have specific size or less, such as, have and be less than about 5mm, be less than about 2mm, be less than about 1mm, be less than about 500 microns, be less than about 200 microns, be less than about 100 microns, be less than about 60 microns, be less than about 50 microns, be less than about 40 microns, be less than about 30 microns, be less than about 25 microns, be less than about 10 microns, be less than about 3 microns, be less than about 1 micron, be less than about 300nm, be less than about 100nm, be less than about 30nm or be less than about 10nm or the full-size perpendicular to fluid flowing less in some cases.In one embodiment, this passage is capillary tube.

In some cases, this device can comprise one or more room or the storage for keeping fluid.In some cases, this room can be communicated with one or more fluid transport device and/or one or more microfluidic channel fluid.Such as, this device can comprise room for collecting the fluid received from experimenter (such as, so as to store and/or with post analysis), be used for comprising fluid for being transported to experimenter (such as, blood, saline, comprises medicine alternatively, hormone, vitamin, medicament, etc.) room, etc.

After being received by fluid in this device, such as experimenter or another people can remove this device or its part from the skin of experimenter.Such as, whole device can be removed, or the part comprising this device storing storage can be removed from this device, and replaces it with another storage storage alternatively.Therefore, such as, in one embodiment, this device can comprise two or more modules, such as, can cause and fluid be received from skin the first module stored storage, and comprise the second module of memory module.In some cases, comprise the module storing storage to be removed from this device.Other example of module and modular system is discussed below; Be incorporated to overall by reference the U.S. Provisional Patent Application No.61/256 being entitled as " ModularSystemsforApplicationtotheSkin " submitted to 30 days October in 2009 here, other example is discussed in 931.

Then, the fluid of reception can be sent to clinical and/or laboratory facility, such as, to analyze.In certain embodiments, whole device can be sent to clinical and/or laboratory facility; But in other embodiments, only a part for this device can be sent to clinical and/or laboratory facility at (such as, comprise the module storing storage, this storage storage comprises fluid).In some cases, can use any appropriate technology (such as, by mailing, with hands, etc.) transport this fluid.In some cases, this fluid can be given suitable personnel when clinical interview by experimenter.Such as, doctor can specify device as above to be used by experimenter, and when next doctor's interview, the fluid received (such as, being comprised in device or module) can be given this doctor by experimenter.

According to some aspect of the present invention, multiple material and method may be used for forming this device, such as, and microfluidic channel, room etc.Such as, various parts of the present invention can be formed by solid material, and wherein passage can be formed by following approach: the film deposition process, laser manufacture, photoetching technique, the engraving method comprising wet-chemical or plasma process etc. of micro-machined, such as spin coating and chemical vapour desposition.See people such as such as ScientificAmerican, 248:44-55,1983(Angell).

In one group of embodiment, the various parts of system of the present invention and device can be formed by polymer, such as, such as polydimethylsiloxane (" PDMS "), politef (" PTFE " or ) etc. elastomer polymer.Such as, according to an embodiment, manufacture fluid system discretely by using PDMS or other soft lithography can realize microfluidic channel and (be suitable for the details of the soft lithography of this embodiment with reference to following documents: the name being disclosed in the 28th volume 153-184 in theAnnualReviewofMaterialScience by YounanXiaandGeorgeM.Whitesides in 1998 is called " SoftLithography ", with by GeorgeM.Whitesides, EmanueleOstuni, ShuichiTakayama, the name that XingyuJiangandDonaldE.Ingber is disclosed in the 3rd volume 335-373 page in theAnnualReviewofBiomedicalEngineering in calendar year 2001 is called " SoftLithographyinBiologyandBiochemistry ", each of these lists of references is incorporated herein by reference).

Other example of the polymer that may be applicable to includes but not limited to polyethylene terephthalate (PET), polyacrylate, polymethacrylates, Merlon, polystyrene, polyethylene, polypropylene, polrvinyl chloride, cyclic olefine copolymer (COC), politef, fluorinated polymer, the silicones of such as polydimethylsiloxane, polyvinylidene chloride, dibenzo cyclobutane (" BCB "), polyimides, the fluorinated derivatives of polyimides, etc.Also can predict relate to the polymer comprising those polymer above-mentioned combination, copolymer or mixture.This device also can be formed by composite, such as, and the composite of polymer and semi-conducting material.

In certain embodiments, various parts of the present invention are by polymeric material and/or flexible material and/or elastomeric material manufacture, and can be formed by hardenable fluid easily, promote the manufacture by molded (such as, copying molded, injection-molded, casting die etc.).Hardenable fluid can be can be caused solidification or spontaneous cure is any fluid of solid substantially, and described solid can comprise and/or transport the fluid of expecting for fluid network.In one embodiment, hardenable fluid comprises polymeric liquid or liquid polymer precursor (that is, " prepolymer ").Its mixture more than suitable polymeric liquid can comprise such as thermoplastic polymer, thermosetting polymer, wax, metal or be heated to their fusing point or complex.As another example, suitable polymeric liquid can comprise the solution of the one or more of polymer in suitable solvent, and this solution forms solid polymeric material when removing solvent (such as, by evaporation).Can know to those skilled in the art from such as melting state or this polymeric material being evaporated by solvent and solidify.Multiple polymers material (wherein many is elastomers) is suitable, and is also applicable to for forming mould or mould mother matrix (embodiment for one or all two mould mother matrix is made up of elastomeric material).The non-limiting inventory of the example of this polymer comprises regular grade silicon resin copolymer, epoxide resin polymer, and acrylate polymer.Epoxide resin polymer is characterized as being the three-membered ring ether that existence is commonly referred to epoxy radicals, 1,2-epoxide or oxirane.Such as, except the compound based on aromatic amine, triazine and cycloaliphatic backbone, the diglycidyl ether of bisphenol-A can be used.Another example comprises the novolac polymer known.The non-limitative example of the silicone elastomer be suitable for according to the present invention comprises those that formed by the precursor comprising chlorosilane, and this chlorosilane is methylchlorosilane, chlorotriethyl silane, phenyl chlorosilane etc. such as.

Silicon resin copolymer is used for some embodiment, such as, and silicone elastomer polydimethylsiloxane.The non-limitative example of PDMS polymer comprises those polymer sold with trade mark Sylgard by DowChemicalCo., Midland, MI, and Sylgard182, Sylgard184 in particular, and Sylgard186.The silicon resin copolymer comprising PDMS has several beneficial properties of the manufacture simplifying microfluidic structures of the present invention.Such as, this material is cheap, easily obtains, and can solidify by hardening by heat from prepolymer liquid.Such as, PDMS typically can harden by prepolymer liquid being exposed to the constant temperature open-assembly time of such as about 1 hour of such as about 65 DEG C to about 75 DEG C.And the silicon resin copolymer of such as PDMS can be elastic and therefore may be used for being formed the very little feature with relatively high aspect ratio necessary in certain embodiments of the present invention.In this, flexible (such as, elastic) mould or mother matrix may be favourable.

The advantage forming the structure of such as microfluidic structures of the present invention from the silicon resin copolymer of such as PDMS be this polymer can oxidized (such as, by be exposed to such as air plasma containing oxygen plasma) make the structure be oxidized comprise chemical group on their surface, this chemical group can be linked to the surface of silicon resin copolymer surface of other oxidation or the oxidation to other polymer multiple and non-polymer material.Therefore, parts can be manufactured and oxidized subsequently and be substantially irreversibly sealed other silicon resin copolymer surface, or to can with the surface of other substrate of the silicon resin copolymer surface reaction of oxidation, and do not need the binding agent that is separated or other sealing device.In majority of case, touch another surface only by making the silicone surface of oxidation and can complete sealing, and do not need to apply aux. pressure to form sealing.In other words, preoxidized silicone surface serves as the contact adhesive for suitable matching surface.Especially, except being irreversibly sealed except self, the silicones of the oxidation of the PDMS be such as oxidized also can be irreversibly sealed the material of a series of oxidations except self, the material of this series of oxidation comprises such as glass, silicon, silicon dioxide, quartz, silicon nitride, polyethylene, polystyrene, vitreous carbon and epoxy polymer, they are oxidized in the mode (such as, by being exposed to containing oxygen plasma) being similar to PDMS surface.Oxidation useful in the present case and encapsulating method and overall molding technique are described in the prior art, such as at Anal.Chem., 70:474-480, the people such as 1998(Duffy) be entitled as in the paper of " RapidPrototypingofMicrofluidicSystemsandPolydimethylsilo xane ", this paper is incorporated herein by reference.

Another advantage being formed microfluidic structures of the present invention (or surface of interior contact fluid) by the silicon resin copolymer be oxidized is that these surfaces can be much more hydrophilic than the surface of typical elastomeric polymer (wishing hydrophilic interior surface in this case).Therefore, this hydrophilic channel surface more easily can be filled and moistening by aqueous solution than the structure be made up of typical unoxidized elastomer polymer or other hydrophobic material.

As described herein, any method of multiple signalling with analyzing and associating or display packing can be provided in one group of embodiment, comprise by vision, signaled by abnormal smells from the patient, sound, sense of touch, the sense of taste etc.Signal structure or generator include but not limited to the room (such as, comprising volatile chemical), machinery, heater, cooler etc. of display device (sighting device, LED, lamp etc.), speaker, release chemical substance.In some cases, signal structure or generator can be integral (such as with this device, with be used for the supporting construction of the skin being applied to experimenter and be integrally connected, such as, this supporting construction comprises the fluid transport device of such as pin or microneedle), or this signal structure integrally can not be connected with this supporting construction.As used herein, " signal structure " or " signal generator " is any equipment that can produce the signal relevant with the state of medium.Such as, this medium can be the body fluid of such as blood or interstitial fluid.

On the other hand, the present invention relates to one or more the tool set comprising aforesaid ingredients, such as, comprise the tool set for conveyance fluid and/or the device from skin reception fluid, comprise the tool set that can produce the device of the aggregation zone of fluid in the skin of experimenter, comprise the tool set of the device can determining fluid, etc.As used herein, " tool set " typically limits encapsulation or the assembly of one or more and/or other device of associating with the present invention or the composition comprising device of the present invention or composition, such as, as described previously.Such as, in one group of embodiment, this tool set can comprise device and one or more composition for this device.Can in liquid form (such as, with solution) or in solid form (such as, dry powder) each (if existence) of the composition of this tool set is provided.In some cases, some compositions can be interchangeable or in addition accessible (such as, to activity form), such as, by adding suitable solvent or other material, this solvent or other material can or can not provide together with this tool set.Other composition related to the present invention or the example of parts include but not limited to solvent, surfactant, diluent, salt, buffer agent, emulsifying agent, chelating agen, filler, antioxidant, binding agent, extender, antiseptic, desiccant, antibacterial, pin, syringe, encapsulating material, pipe, bottle, flask, beaker, plate, frit, filter, ring, fixture, overcoat, sticking patch, container, adhesive tape, binding agent etc., such as to use, management, amendment, assembling, store, encapsulation, preparation, mixing, dilute and/or preserve this composition for special-purpose, such as sample and/or experimenter.

In some cases, tool set of the present invention can comprise operation instruction in any form, provides this operation instruction to make to those skilled in the art will recognize that this operation instruction will associate with composition of the present invention in conjunction with composition of the present invention.Such as, this operation instruction can comprise this composition and/or the use of other composition of associating with this tool set, amendment, mixing, dilution, preservation, management, assembling, storage, encapsulation and/or preparation operation instruction.In some cases, this operation instruction also can comprise the conveying of this composition and/or the operation instruction of management, such as, for special-purpose (such as, for sample and/or experimenter).Any form of the suitable carrier that this operation instruction can be identified as comprising this operation instruction with those skilled in the art is by any way provided, such as, written or that publish, oral, can hear (such as, phone), numeral, optics, (such as, video-tape, DVD etc.) or the electronic communication (comprising the Internet or network communication) of vision.

In certain embodiments, the present invention relates to the method for sales promotion one or more embodiment of the present invention as discussed here.As used herein, " sales promotion " comprises all methods of trade, the sale including but not limited to associate with system of the present invention as discussed here, device, equipment, article, method, composition, tool set etc., advertisement, trust, license, contract, indicate, educate, study, import, outlet, negotiation, financing, loan, trade, sale, profiteering, distribution, repairing, replacing, insurance, the method for accusing, to apply for a patent etc.Promotion approach can be performed by any group, and described any group includes but not limited to personal group, enterprise (public or individual), partnership business, company, trust, the educational institution of contract or sub-contract agent, such as institute and university, research institution, hospital or other Clinical Institutions, government bodies etc.Advertising campaign can comprise clearly associate with the present invention any type of communication (such as, the communication of written, oral and/or electronics, such as, but not limited to Email, phone, the Internet, network etc.).

In one group of embodiment, promotion approach can relate to one or more operation instruction.As used herein, " operation instruction " can limit the ingredient of marking tools (such as, guidance, guiding, warning, label, annotation, FAQ or " FAQs " etc.), and typically relate to about the present invention or with the present invention and/or the written operation instruction with encapsulated association of the present invention.Operation instruction can also comprise in any type of instruction communication (such as, oral, electronics, can listen, numeral, optics, vision etc.), this instruction communication be provided by any way user will clearly be identified this operation instruction will associate with the present invention, such as, as discussed here.

Incorporated herein by reference with Publication about Document: at the U.S. Patent application No.12/478 being entitled as " CompositionsandMethodsforRapidOne-StepDiagnosis " of the D.Levinson that the 4 days June in 2009 being published as U.S. Patent Application Publication No.2010/0069726 on March 18th, 2010 submits to, 756; Within 2009, December is published as the international patent application No.PCT/US09/046333 being entitled as " CompositionsandMethodsforRapidOne-StepDiagnosis " of the D.Levinson of the submission in 4 days June in 2009 of WO2009/149308 on the 10th; The U.S. Patent application No.12/716 being entitled as " SystemsandMethodsforCreatingandUsingSuctionBlistersorOth erPooledRegionsofFluidwithintheSkin " of the people such as the Levinson that on March 2nd, 2010 submits to, 233; The U.S. Patent application No.12/716 being entitled as " OxygenSensor " of the people such as the Levinson that on March 2nd, 2010 submits to, 222; The U.S. Patent application No.12/716 being entitled as " DevicesandTechniquesAssociatedwithDiagnostics; Therapies; andOtherApplications; IncludingSkin-AssociatedApplications " of the people such as the Bernstein that on March 2nd, 2010 submits to, 229; The U.S. Patent application No.12/716 being entitled as " TechniquesandDevicesAssociatedwithBloodSampling " of the people such as the Levinson that on March 2nd, 2010 submits to, 226; The U.S. Provisional Patent Application No.61/294 being entitled as " BloodSamplingDeviceandMethod " of the people such as the Chickering that on January 13rd, 2010 submits to, 543; The U.S. Provisional Patent Application No.61/334 being entitled as " RapidDeliveryand/orWithdrawalofFluids " of the people such as the Chickering that on May 13rd, 2010 submits to, 533; With the U.S. Provisional Patent Application No.61/334 being entitled as " SamplingDeviceInterfaces " of the people such as Chickering submitted on May 13rd, 2010,529.In addition, the U.S. Provisional Patent Application No.61/365 being entitled as " Low-PressurePackagingforFluidDevices " of the Schott that on July 16th, 2010 submits to, 196 is incorporated herein by reference.

Although here described and several embodiment of the present invention be shown, but easily anticipation is used for performing described function and/or obtains other device multiple and/or the structure of described result and/or one or more advantage described herein by those skilled in the art, and each of this change and/or amendment is considered within the scope of the invention.More generally, those skilled in the art will easily understand, all parameters described herein, size, material and structure are meant to be exemplary, and the parameter of reality, size, material and/or structure will depend on application-specific, and instruction of the present invention is used for this application-specific.Those skilled in the art will recognize that or can only use normal experiment to find out many equivalents of specific embodiment of the present invention described herein.Therefore, should be appreciated that previous embodiment is presented by means of only the mode of example, and in the scope of claims and equivalent thereof, can with specifically described and claimed differently enforcement the present invention.The present invention relates to each single feature, system, article, material, tool set and/or method described herein.In addition, if this feature, system, article, material, tool set and/or method are not conflicting, then many combinations of two or more this feature, system, article, material, tool set and/or methods are included within the scope of the invention.

As all definition limited here and use are appreciated that domination dictionary definition, the usual implication of the definition in the document be incorporated to by reference and/or the term of restriction.

Mean " at least one " as being appreciated that at description and the word " " used in the claims and " one " here, unless clearly specified contrary.

Mean as being appreciated that with the phrase "and/or" used in the claims in the description here " any one or both " of the key element be so connected, that is, to be present in combination in certain situation and the key element be present in discretely in other situation.The multiple key elements listed with "and/or" should be explained in an identical manner, that is, " one or more " of the key element so connected.Except the key element identified especially by "and/or" subordinate clause, or incoherent other key element relevant to those key elements identified especially can exist alternatively.Therefore, as non-limitative example, can only refer to that A(comprises the key element except B alternatively in one embodiment to quoting of " A and/or B " when combining the open language such as " comprised " and using); Only refer to that B(comprises the key element except A alternatively in other embodiments); Refer to A and B (comprising other key element alternatively) in another embodiment; Etc..

As used herein in the specification and in the claims of the, "or" is appreciated that to have the implication identical with the "and/or" such as limited above.Such as, when being separated the project in inventory, "or" or "and/or" should be interpreted as comprising property, that is, comprise at least one, but also comprise the more than one of many or a series of key element, and comprise other unlisted project alternatively.Only clearly indicate contrary project (such as " only " or " just what a ", or when with time in the claims, " by ... composition ") just what a key element comprising many or a series of key element will be referred to.Usually, term "or" as used herein is worked as exclusiveness term (such as " arbitrary ", " one ", " only one ", or " just what a ") after time only should be interpreted as instruction exclusiveness substitute (that is, " one or the other but be not both ")." substantially by ... composition " is when with having in as Patent Law field its usual implication used time in the claims.

As used herein in the specification and in the claims of the, phrase " at least one " about one or more key element a series of is appreciated that at least one key element meaning to be selected from any one in this series of key element or more key element, but is not necessarily included at least one of each and each key element specifically listed in this series of key element and does not get rid of any combination of the key element in this series of key element.This definition also allows the key element outside the key element of concrete mark in a series of key elements of " at least one " indication unless a term to exist alternatively, no matter relevant or uncorrelated to those key elements specifically identified.Therefore, as non-limitative example, " A and B at least one " (or equally, " A or B at least one ", or equally, " A and/or B at least one ") at least one A can be referred in one embodiment, comprise more than one A alternatively, there is not B(and comprise the key element except B alternatively); In another embodiment, refer at least one B, comprise more than one B alternatively there is not A(and comprise the key element except A alternatively); In another embodiment, refer to that at least one A(comprises more than one A alternatively) and at least one B(comprise more than one B alternatively) (and comprising other key element alternatively); Etc..

Also should be appreciated that contrary unless clearly indicated, comprise in any method claimed here of more than one step or action, the step of the method or the order of action are not necessarily limited to the step of the method enumerated or the order of action.

In the claims, and in superincumbent description, such as " comprise ", " comprising ", " with ", " having ", " containing ", " relating to ", " having ", " by ... form " etc. all conjunctions to be understood to open, that is, mean to include but not limited to.Illustrate in chapters and sections 2111.03 as USPO's patent examining procedure handbook, only conjunction " by ... composition " and " substantially by ... form " should be closed or semi-enclosed conjunction respectively.

Claims

1., for encapsulating article for the device comprising mass transfer parts, described article comprise:

Pressure is less than the environment of below atmospheric pressure 50mmHg, described environment comprises the described device of described mass transfer parts, described mass transfer parts are used for from the skin of experimenter and/or receive material below described skins, and/or are used for transportation of substances to the described skin of experimenter and/or the position below described skin.

2. article according to claim 1, wherein, described environment is comprised in outer enclosure.

3. article according to claim 2, wherein, described outer enclosure be can manual deformation at least partially.

4. article according to claim 2, wherein, described outer enclosure be rigidity at least partially.

5. the article described in any one in claim 2-4, wherein, described device is molded in described outer enclosure by described outer enclosure substantially.

6. the article described in any one in claim 2-4, wherein, described outer enclosure comprises glass.

7. the article described in any one in claim 2-4, wherein, described outer enclosure comprises polyethylene.

8. the article described in any one in claim 2-4, wherein, described outer enclosure comprises Merlon.

9. the article described in any one in claim 2-4, wherein, described outer enclosure comprises metal.

10. the article described in any one in claim 2-4, wherein, described outer enclosure comprises aluminum.

Article described in any one in 11. claim 2-4, wherein, described outer enclosure comprises laminates.

Article described in any one in 12. claim 2-4, wherein, described outer enclosure comprises mylar.

Article described in any one in 13. claim 1-4, wherein, described pressure is less than below atmospheric pressure 100mmHg.

Article described in any one in 14. claim 1-4, wherein, described pressure is less than below atmospheric pressure 200mmHg.

Article described in any one in 15. claim 1-4, wherein, described pressure is less than below atmospheric pressure 300mmHg.

Article described in any one in 16. claim 1-4, wherein, described pressure is less than below atmospheric pressure 500mmHg.

Article described in any one in 17. claim 1-4, wherein, described pressure is less than below atmospheric pressure 700mmHg.

Article described in any one in 18. claim 1-4, wherein, described pressure is less than below atmospheric pressure 750mmHg.

Article described in any one in 19. claim 1-4, wherein, described environment is substantially aseptic.

Article described in any one in 20. claim 1-4, wherein, described device comprises vacuum chamber, and described vacuum chamber has the internal pressure being less than atmospheric pressure.

21. article according to claim 20, wherein, described internal pressure is less than below atmospheric pressure 50mmHg.

22. article according to claim 20, wherein, described internal pressure is less than below atmospheric pressure 100mmHg.

23. article according to claim 20, wherein, described internal pressure is less than below atmospheric pressure 200mmHg.

24. article according to claim 20, wherein, described internal pressure is less than below atmospheric pressure 300mmHg.

25. article according to claim 20, wherein, described internal pressure is less than below atmospheric pressure 500mmHg.

26. article according to claim 20, wherein, described internal pressure is less than below atmospheric pressure 700mmHg.

27. article according to claim 20, wherein, the internal pressure of the described vacuum chamber in described device is substantially equal to the pressure of the described environment surrounding described device.

Article described in any one in 28. claim 2-4, wherein, described mass transfer parts comprise one or more skin and insert object.

29. article according to claim 28, wherein, one or more skin described inserts object and comprises one or more microneedle.

30. article according to claim 29, wherein, at least some of described microneedle is solid.

31. article according to claim 29, wherein, at least some of described microneedle is hollow.

32. article according to claim 29, wherein, described device also comprises activation members, and described activation members is used for that skin is inserted object and is inserted in the skin of experimenter.

33. article according to claim 32, wherein, described outer enclosure comprises the rigid material at least surrounding described activation members.

34. 1 kinds for encapsulating the method for the device comprising mass transfer parts, described method comprises:

Device is exposed to environment, described environment has the pressure being less than below atmospheric pressure 50mmHg, wherein said device comprises described mass transfer parts, described mass transfer parts are used for from the skin of experimenter and/or receive material below described skins, and/or are used for substance use to the skin of experimenter and/or the position below described skin.

35. methods according to claim 34, wherein, described environment is comprised in outer enclosure.

36. methods according to claim 35, wherein, described outer enclosure be can manual deformation at least partially.

37. methods according to claim 35, wherein, described outer enclosure be rigidity at least partially.

38. methods according to claim 35, wherein, described device is molded in described outer enclosure by described outer enclosure substantially.

39. methods according to claim 34, wherein, described mass transfer parts comprise one or more skin and insert object.

40. methods according to claim 39, wherein, one or more skin described inserts object and comprises one or more microneedle.

41. 1 kinds for encapsulating the article of the device comprising pin and vacuum chamber, described article comprise:

Pressure is less than the environment of below atmospheric pressure 50mmHg, and described environment comprises the described device of described pin and vacuum chamber, and described vacuum chamber has the internal pressure being less than atmospheric pressure.

42. article according to claim 41, wherein, described environment is comprised in outer enclosure.

43. article according to claim 42, wherein, described outer enclosure be can manual deformation at least partially.

44. article according to claim 42, wherein, described outer enclosure be rigidity at least partially.

45. article according to claim 42, wherein, described device is molded in described outer enclosure by described outer enclosure substantially.